Serveur d'exploration sur la rapamycine et les champignons

Attention, ce site est en cours de développement !
Attention, site généré par des moyens informatiques à partir de corpus bruts.
Les informations ne sont donc pas validées.

Rapamycin antifungal action is mediated via conserved complexes with FKBP12 and TOR kinase homologs in Cryptococcus neoformans.

Identifieur interne : 001A54 ( Main/Exploration ); précédent : 001A53; suivant : 001A55

Rapamycin antifungal action is mediated via conserved complexes with FKBP12 and TOR kinase homologs in Cryptococcus neoformans.

Auteurs : M C Cruz [États-Unis] ; L M Cavallo ; J M Görlach ; G. Cox ; J R Perfect ; M E Cardenas ; J. Heitman

Source :

RBID : pubmed:10330150

Descripteurs français

English descriptors

Abstract

Cryptococcus neoformans is a fungal pathogen that causes meningitis in patients immunocompromised by AIDS, chemotherapy, organ transplantation, or high-dose steroids. Current antifungal drug therapies are limited and suffer from toxic side effects and drug resistance. Here, we defined the targets and mechanisms of antifungal action of the immunosuppressant rapamycin in C. neoformans. In the yeast Saccharomyces cerevisiae and in T cells, rapamycin forms complexes with the FKBP12 prolyl isomerase that block cell cycle progression by inhibiting the TOR kinases. We identified the gene encoding a C. neoformans TOR1 homolog. Using a novel two-hybrid screen for rapamycin-dependent TOR-binding proteins, we identified the C. neoformans FKBP12 homolog, encoded by the FRR1 gene. Disruption of the FKBP12 gene conferred rapamycin and FK506 resistance but had no effect on growth, differentiation, or virulence of C. neoformans. Two spontaneous mutations that confer rapamycin resistance alter conserved residues on TOR1 or FKBP12 that are required for FKBP12-rapamycin-TOR1 interactions or FKBP12 stability. Two other spontaneous mutations result from insertion of novel DNA sequences into the FKBP12 gene. Our observations reveal that the antifungal activities of rapamycin and FK506 are mediated via FKBP12 and TOR homologs and that a high proportion of spontaneous mutants in C. neoformans result from insertion of novel DNA sequences, and they suggest that nonimmunosuppressive rapamycin analogs have potential as antifungal agents.

DOI: 10.1128/mcb.19.6.4101
PubMed: 10330150
PubMed Central: PMC104369


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

<record>
<TEI>
<teiHeader>
<fileDesc>
<titleStmt>
<title xml:lang="en">Rapamycin antifungal action is mediated via conserved complexes with FKBP12 and TOR kinase homologs in Cryptococcus neoformans.</title>
<author>
<name sortKey="Cruz, M C" sort="Cruz, M C" uniqKey="Cruz M" first="M C" last="Cruz">M C Cruz</name>
<affiliation wicri:level="1">
<nlm:affiliation>Departments of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Genetics, Duke University Medical Center, Durham, North Carolina 27710</wicri:regionArea>
<wicri:noRegion>North Carolina 27710</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Cavallo, L M" sort="Cavallo, L M" uniqKey="Cavallo L" first="L M" last="Cavallo">L M Cavallo</name>
</author>
<author>
<name sortKey="Gorlach, J M" sort="Gorlach, J M" uniqKey="Gorlach J" first="J M" last="Görlach">J M Görlach</name>
</author>
<author>
<name sortKey="Cox, G" sort="Cox, G" uniqKey="Cox G" first="G" last="Cox">G. Cox</name>
</author>
<author>
<name sortKey="Perfect, J R" sort="Perfect, J R" uniqKey="Perfect J" first="J R" last="Perfect">J R Perfect</name>
</author>
<author>
<name sortKey="Cardenas, M E" sort="Cardenas, M E" uniqKey="Cardenas M" first="M E" last="Cardenas">M E Cardenas</name>
</author>
<author>
<name sortKey="Heitman, J" sort="Heitman, J" uniqKey="Heitman J" first="J" last="Heitman">J. Heitman</name>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">PubMed</idno>
<date when="1999">1999</date>
<idno type="RBID">pubmed:10330150</idno>
<idno type="pmid">10330150</idno>
<idno type="pmc">PMC104369</idno>
<idno type="doi">10.1128/mcb.19.6.4101</idno>
<idno type="wicri:Area/Main/Corpus">001A56</idno>
<idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001A56</idno>
<idno type="wicri:Area/Main/Curation">001A56</idno>
<idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">001A56</idno>
<idno type="wicri:Area/Main/Exploration">001A56</idno>
</publicationStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en">Rapamycin antifungal action is mediated via conserved complexes with FKBP12 and TOR kinase homologs in Cryptococcus neoformans.</title>
<author>
<name sortKey="Cruz, M C" sort="Cruz, M C" uniqKey="Cruz M" first="M C" last="Cruz">M C Cruz</name>
<affiliation wicri:level="1">
<nlm:affiliation>Departments of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Genetics, Duke University Medical Center, Durham, North Carolina 27710</wicri:regionArea>
<wicri:noRegion>North Carolina 27710</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Cavallo, L M" sort="Cavallo, L M" uniqKey="Cavallo L" first="L M" last="Cavallo">L M Cavallo</name>
</author>
<author>
<name sortKey="Gorlach, J M" sort="Gorlach, J M" uniqKey="Gorlach J" first="J M" last="Görlach">J M Görlach</name>
</author>
<author>
<name sortKey="Cox, G" sort="Cox, G" uniqKey="Cox G" first="G" last="Cox">G. Cox</name>
</author>
<author>
<name sortKey="Perfect, J R" sort="Perfect, J R" uniqKey="Perfect J" first="J R" last="Perfect">J R Perfect</name>
</author>
<author>
<name sortKey="Cardenas, M E" sort="Cardenas, M E" uniqKey="Cardenas M" first="M E" last="Cardenas">M E Cardenas</name>
</author>
<author>
<name sortKey="Heitman, J" sort="Heitman, J" uniqKey="Heitman J" first="J" last="Heitman">J. Heitman</name>
</author>
</analytic>
<series>
<title level="j">Molecular and cellular biology</title>
<idno type="ISSN">0270-7306</idno>
<imprint>
<date when="1999" type="published">1999</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Amino Acid Sequence (MeSH)</term>
<term>Animals (MeSH)</term>
<term>Antifungal Agents (pharmacology)</term>
<term>Base Sequence (MeSH)</term>
<term>Blotting, Southern (MeSH)</term>
<term>Blotting, Western (MeSH)</term>
<term>Cell Survival (MeSH)</term>
<term>Cloning, Molecular (MeSH)</term>
<term>Conserved Sequence (MeSH)</term>
<term>Cryptococcus neoformans (drug effects)</term>
<term>Disease Models, Animal (MeSH)</term>
<term>Drosophila Proteins (MeSH)</term>
<term>Female (MeSH)</term>
<term>Immunophilins (metabolism)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred BALB C (MeSH)</term>
<term>Models, Genetic (MeSH)</term>
<term>Molecular Sequence Data (MeSH)</term>
<term>Mutagenesis, Site-Directed (MeSH)</term>
<term>Protein Binding (MeSH)</term>
<term>Rabbits (MeSH)</term>
<term>Receptor Protein-Tyrosine Kinases (metabolism)</term>
<term>Recombination, Genetic (MeSH)</term>
<term>Saccharomyces cerevisiae (drug effects)</term>
<term>Sequence Homology, Amino Acid (MeSH)</term>
<term>Sirolimus (pharmacology)</term>
<term>Tacrolimus Binding Proteins (MeSH)</term>
<term>Time Factors (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Animaux (MeSH)</term>
<term>Antifongiques (pharmacologie)</term>
<term>Clonage moléculaire (MeSH)</term>
<term>Cryptococcus neoformans (effets des médicaments et des substances chimiques)</term>
<term>Données de séquences moléculaires (MeSH)</term>
<term>Facteurs temps (MeSH)</term>
<term>Femelle (MeSH)</term>
<term>Immunophilines (métabolisme)</term>
<term>Lapins (MeSH)</term>
<term>Liaison aux protéines (MeSH)</term>
<term>Modèles animaux de maladie humaine (MeSH)</term>
<term>Modèles génétiques (MeSH)</term>
<term>Mutagenèse dirigée (MeSH)</term>
<term>Protéines de Drosophila (MeSH)</term>
<term>Protéines de liaison au tacrolimus (MeSH)</term>
<term>Recombinaison génétique (MeSH)</term>
<term>Récepteurs à activité tyrosine kinase (métabolisme)</term>
<term>Saccharomyces cerevisiae (effets des médicaments et des substances chimiques)</term>
<term>Similitude de séquences d'acides aminés (MeSH)</term>
<term>Sirolimus (pharmacologie)</term>
<term>Souris (MeSH)</term>
<term>Souris de lignée BALB C (MeSH)</term>
<term>Survie cellulaire (MeSH)</term>
<term>Séquence conservée (MeSH)</term>
<term>Séquence d'acides aminés (MeSH)</term>
<term>Séquence nucléotidique (MeSH)</term>
<term>Technique de Southern (MeSH)</term>
<term>Technique de Western (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Immunophilins</term>
<term>Receptor Protein-Tyrosine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en">
<term>Antifungal Agents</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Cryptococcus neoformans</term>
<term>Saccharomyces cerevisiae</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr">
<term>Cryptococcus neoformans</term>
<term>Saccharomyces cerevisiae</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Immunophilines</term>
<term>Récepteurs à activité tyrosine kinase</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr">
<term>Antifongiques</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Base Sequence</term>
<term>Blotting, Southern</term>
<term>Blotting, Western</term>
<term>Cell Survival</term>
<term>Cloning, Molecular</term>
<term>Conserved Sequence</term>
<term>Disease Models, Animal</term>
<term>Drosophila Proteins</term>
<term>Female</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Models, Genetic</term>
<term>Molecular Sequence Data</term>
<term>Mutagenesis, Site-Directed</term>
<term>Protein Binding</term>
<term>Rabbits</term>
<term>Recombination, Genetic</term>
<term>Sequence Homology, Amino Acid</term>
<term>Tacrolimus Binding Proteins</term>
<term>Time Factors</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Clonage moléculaire</term>
<term>Données de séquences moléculaires</term>
<term>Facteurs temps</term>
<term>Femelle</term>
<term>Lapins</term>
<term>Liaison aux protéines</term>
<term>Modèles animaux de maladie humaine</term>
<term>Modèles génétiques</term>
<term>Mutagenèse dirigée</term>
<term>Protéines de Drosophila</term>
<term>Protéines de liaison au tacrolimus</term>
<term>Recombinaison génétique</term>
<term>Similitude de séquences d'acides aminés</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Survie cellulaire</term>
<term>Séquence conservée</term>
<term>Séquence d'acides aminés</term>
<term>Séquence nucléotidique</term>
<term>Technique de Southern</term>
<term>Technique de Western</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Cryptococcus neoformans is a fungal pathogen that causes meningitis in patients immunocompromised by AIDS, chemotherapy, organ transplantation, or high-dose steroids. Current antifungal drug therapies are limited and suffer from toxic side effects and drug resistance. Here, we defined the targets and mechanisms of antifungal action of the immunosuppressant rapamycin in C. neoformans. In the yeast Saccharomyces cerevisiae and in T cells, rapamycin forms complexes with the FKBP12 prolyl isomerase that block cell cycle progression by inhibiting the TOR kinases. We identified the gene encoding a C. neoformans TOR1 homolog. Using a novel two-hybrid screen for rapamycin-dependent TOR-binding proteins, we identified the C. neoformans FKBP12 homolog, encoded by the FRR1 gene. Disruption of the FKBP12 gene conferred rapamycin and FK506 resistance but had no effect on growth, differentiation, or virulence of C. neoformans. Two spontaneous mutations that confer rapamycin resistance alter conserved residues on TOR1 or FKBP12 that are required for FKBP12-rapamycin-TOR1 interactions or FKBP12 stability. Two other spontaneous mutations result from insertion of novel DNA sequences into the FKBP12 gene. Our observations reveal that the antifungal activities of rapamycin and FK506 are mediated via FKBP12 and TOR homologs and that a high proportion of spontaneous mutants in C. neoformans result from insertion of novel DNA sequences, and they suggest that nonimmunosuppressive rapamycin analogs have potential as antifungal agents.</div>
</front>
</TEI>
<pubmed>
<MedlineCitation Status="MEDLINE" Owner="NLM">
<PMID Version="1">10330150</PMID>
<DateCompleted>
<Year>1999</Year>
<Month>06</Month>
<Day>17</Day>
</DateCompleted>
<DateRevised>
<Year>2019</Year>
<Month>05</Month>
<Day>23</Day>
</DateRevised>
<Article PubModel="Print">
<Journal>
<ISSN IssnType="Print">0270-7306</ISSN>
<JournalIssue CitedMedium="Print">
<Volume>19</Volume>
<Issue>6</Issue>
<PubDate>
<Year>1999</Year>
<Month>Jun</Month>
</PubDate>
</JournalIssue>
<Title>Molecular and cellular biology</Title>
<ISOAbbreviation>Mol Cell Biol</ISOAbbreviation>
</Journal>
<ArticleTitle>Rapamycin antifungal action is mediated via conserved complexes with FKBP12 and TOR kinase homologs in Cryptococcus neoformans.</ArticleTitle>
<Pagination>
<MedlinePgn>4101-12</MedlinePgn>
</Pagination>
<Abstract>
<AbstractText>Cryptococcus neoformans is a fungal pathogen that causes meningitis in patients immunocompromised by AIDS, chemotherapy, organ transplantation, or high-dose steroids. Current antifungal drug therapies are limited and suffer from toxic side effects and drug resistance. Here, we defined the targets and mechanisms of antifungal action of the immunosuppressant rapamycin in C. neoformans. In the yeast Saccharomyces cerevisiae and in T cells, rapamycin forms complexes with the FKBP12 prolyl isomerase that block cell cycle progression by inhibiting the TOR kinases. We identified the gene encoding a C. neoformans TOR1 homolog. Using a novel two-hybrid screen for rapamycin-dependent TOR-binding proteins, we identified the C. neoformans FKBP12 homolog, encoded by the FRR1 gene. Disruption of the FKBP12 gene conferred rapamycin and FK506 resistance but had no effect on growth, differentiation, or virulence of C. neoformans. Two spontaneous mutations that confer rapamycin resistance alter conserved residues on TOR1 or FKBP12 that are required for FKBP12-rapamycin-TOR1 interactions or FKBP12 stability. Two other spontaneous mutations result from insertion of novel DNA sequences into the FKBP12 gene. Our observations reveal that the antifungal activities of rapamycin and FK506 are mediated via FKBP12 and TOR homologs and that a high proportion of spontaneous mutants in C. neoformans result from insertion of novel DNA sequences, and they suggest that nonimmunosuppressive rapamycin analogs have potential as antifungal agents.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Cruz</LastName>
<ForeName>M C</ForeName>
<Initials>MC</Initials>
<AffiliationInfo>
<Affiliation>Departments of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Cavallo</LastName>
<ForeName>L M</ForeName>
<Initials>LM</Initials>
</Author>
<Author ValidYN="Y">
<LastName>Görlach</LastName>
<ForeName>J M</ForeName>
<Initials>JM</Initials>
</Author>
<Author ValidYN="Y">
<LastName>Cox</LastName>
<ForeName>G</ForeName>
<Initials>G</Initials>
</Author>
<Author ValidYN="Y">
<LastName>Perfect</LastName>
<ForeName>J R</ForeName>
<Initials>JR</Initials>
</Author>
<Author ValidYN="Y">
<LastName>Cardenas</LastName>
<ForeName>M E</ForeName>
<Initials>ME</Initials>
</Author>
<Author ValidYN="Y">
<LastName>Heitman</LastName>
<ForeName>J</ForeName>
<Initials>J</Initials>
</Author>
</AuthorList>
<Language>eng</Language>
<DataBankList CompleteYN="Y">
<DataBank>
<DataBankName>GENBANK</DataBankName>
<AccessionNumberList>
<AccessionNumber>AF097888</AccessionNumber>
<AccessionNumber>AF097889</AccessionNumber>
<AccessionNumber>AF098972</AccessionNumber>
<AccessionNumber>AF098973</AccessionNumber>
</AccessionNumberList>
</DataBank>
</DataBankList>
<GrantList CompleteYN="Y">
<Grant>
<GrantID>R37 AI039115</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant>
<GrantID>R01 AI039115</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant>
<GrantID>R01 AI41937</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant>
<GrantID>AI41937-S1</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant>
<GrantID>R01 AI39115</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList>
<PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013487">Research Support, U.S. Gov't, P.H.S.</PublicationType>
</PublicationTypeList>
</Article>
<MedlineJournalInfo>
<Country>United States</Country>
<MedlineTA>Mol Cell Biol</MedlineTA>
<NlmUniqueID>8109087</NlmUniqueID>
<ISSNLinking>0270-7306</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000935">Antifungal Agents</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D029721">Drosophila Proteins</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 2.7.10.1</RegistryNumber>
<NameOfSubstance UI="D020794">Receptor Protein-Tyrosine Kinases</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 2.7.10.1</RegistryNumber>
<NameOfSubstance UI="C080148">tor protein, Drosophila</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 5.2.1.-</RegistryNumber>
<NameOfSubstance UI="D022021">Tacrolimus Binding Proteins</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 5.2.1.8</RegistryNumber>
<NameOfSubstance UI="D020104">Immunophilins</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>W36ZG6FT64</RegistryNumber>
<NameOfSubstance UI="D020123">Sirolimus</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<CitationSubset>X</CitationSubset>
<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D000595" MajorTopicYN="N">Amino Acid Sequence</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000935" MajorTopicYN="N">Antifungal Agents</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D001483" MajorTopicYN="N">Base Sequence</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D015139" MajorTopicYN="N">Blotting, Southern</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D015153" MajorTopicYN="N">Blotting, Western</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D002470" MajorTopicYN="N">Cell Survival</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D003001" MajorTopicYN="N">Cloning, Molecular</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D017124" MajorTopicYN="N">Conserved Sequence</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D003455" MajorTopicYN="N">Cryptococcus neoformans</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D029721" MajorTopicYN="Y">Drosophila Proteins</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D020104" MajorTopicYN="N">Immunophilins</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008957" MajorTopicYN="N">Models, Genetic</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008969" MajorTopicYN="N">Molecular Sequence Data</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D016297" MajorTopicYN="N">Mutagenesis, Site-Directed</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D011817" MajorTopicYN="N">Rabbits</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D020794" MajorTopicYN="N">Receptor Protein-Tyrosine Kinases</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D011995" MajorTopicYN="N">Recombination, Genetic</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D012441" MajorTopicYN="N">Saccharomyces cerevisiae</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D017386" MajorTopicYN="N">Sequence Homology, Amino Acid</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D020123" MajorTopicYN="N">Sirolimus</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D022021" MajorTopicYN="N">Tacrolimus Binding Proteins</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData>
<History>
<PubMedPubDate PubStatus="pubmed">
<Year>1999</Year>
<Month>5</Month>
<Day>18</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline">
<Year>1999</Year>
<Month>5</Month>
<Day>18</Day>
<Hour>0</Hour>
<Minute>1</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez">
<Year>1999</Year>
<Month>5</Month>
<Day>18</Day>
<Hour>0</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList>
<ArticleId IdType="pubmed">10330150</ArticleId>
<ArticleId IdType="pmc">PMC104369</ArticleId>
<ArticleId IdType="doi">10.1128/mcb.19.6.4101</ArticleId>
</ArticleIdList>
<ReferenceList>
<Reference>
<Citation>J Biol Chem. 1995 Jan 13;270(2):815-22</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">7822316</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Cell. 1995 Jul 14;82(1):121-30</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">7606777</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Nature. 1995 Oct 5;377(6548):441-6</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">7566123</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Biol Chem. 1995 Nov 17;270(46):27531-7</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">7499212</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>EMBO J. 1995 Dec 1;14(23):5892-907</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8846782</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Clin Microbiol Rev. 1995 Oct;8(4):515-48</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8665468</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>EMBO J. 1996 Feb 1;15(3):658-64</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8599949</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Trends Biotechnol. 1998 Oct;16(10):427-33</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9807840</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>New Biol. 1992 May;4(5):448-60</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">1515410</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Nature. 1992 Dec 17;360(6405):682-4</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">1281518</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Infect Dis. 1993 Jan;167(1):186-90</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8418165</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Mol Biol. 1993 Jan 5;229(1):105-24</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">7678431</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Mol Cell Biol. 1993 Mar;13(3):1962-70</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8441425</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Bacteriol. 1993 Mar;175(5):1405-11</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8444802</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Immunology. 1976 Oct;31(4):631-41</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">824198</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Antibiot (Tokyo). 1979 Jun;32(6):630-45</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">381274</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Am J Pathol. 1980 Oct;101(1):177-94</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">7004196</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Antibiot (Tokyo). 1987 Sep;40(9):1249-55</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">2445721</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Gene. 1989 Apr 15;77(1):51-9</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">2744487</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Nature. 1990 Aug 16;346(6285):671-4</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">1696686</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Nature. 1990 Aug 16;346(6285):674-7</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">1696687</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Mol Cell Biol. 1991 Mar;11(3):1718-23</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">1996117</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1948-52</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">1705713</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Methods Enzymol. 1991;194:3-21</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">2005794</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Science. 1991 May 10;252(5007):839-42</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">1709302</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Science. 1991 Aug 23;253(5022):905-9</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">1715094</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Cell. 1991 Aug 23;66(4):807-15</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">1715244</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Cell. 1992 Mar 20;68(6):1077-90</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">1547504</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Gene. 1992 Apr 1;113(1):125-7</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">1563628</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Immunol Today. 1992 Apr;13(4):136-42</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">1374612</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Cell. 1993 May 7;73(3):585-96</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8387896</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Annu Rev Biophys Biomol Struct. 1993;22:123-42</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">7688608</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Infect Immun. 1993 Oct;61(10):4446-51</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8406836</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Mol Cell Biol. 1993 Oct;13(10):6012-23</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8413204</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Mol Biol Cell. 1994 Jan;5(1):105-18</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8186460</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5372-6</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">7515500</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Nature. 1994 Jun 30;369(6483):756-8</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8008069</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Cell. 1994 Jul 15;78(1):35-43</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">7518356</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12008-12</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">7991574</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Biol Chem. 1994 Dec 23;269(51):32027-30</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">7528205</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12574-8</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">7809080</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Genes Dev. 1996 Feb 1;10(3):279-88</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8595879</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Biochem Soc Trans. 1996 Feb;24(1):234-9</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8674674</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Microbiology. 1996 Jun;142 ( Pt 6):1557-65</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8704997</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Science. 1996 Jul 12;273(5272):239-42</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8662507</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Genes Dev. 1996 Aug 1;10(15):1904-16</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8756348</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Cell. 1996 Aug 23;86(4):517-20</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8752206</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Mol Biol Cell. 1996 Jan;7(1):25-42</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8741837</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13780-5</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8943012</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Genetics. 1996 Dec;144(4):1425-36</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8978031</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Antimicrob Agents Chemother. 1997 Jan;41(1):156-61</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">8980772</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Cell. 1997 Feb 21;88(4):531-42</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9038344</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3070-5</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9096347</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Annu Rev Immunol. 1997;15:707-47</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9143705</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>EMBO J. 1997 May 15;16(10):2576-89</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9184205</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Science. 1997 Jul 4;277(5322):99-101</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9204908</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Mol Cell Biol. 1997 Oct;17(10):5968-75</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9315655</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Bacteriol. 1997 Oct;179(20):6325-34</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9335279</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Biol Chem. 1997 Oct 17;272(42):26457-63</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9334222</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Genes Dev. 1997 Dec 1;11(23):3206-17</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9389652</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Genes Dev. 1997 Dec 15;11(24):3432-44</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9407035</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Genes Dev. 1997 Dec 15;11(24):3445-58</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9407036</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Biol Chem. 1997 Dec 19;272(51):32547-50</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9405468</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Curr Opin Cell Biol. 1997 Dec;9(6):782-7</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9425342</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Biol Chem. 1998 Feb 13;273(7):3963-6</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9461583</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1432-7</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9465032</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Genes Dev. 1998 Feb 15;12(4):502-13</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9472019</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4264-9</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9539725</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7772-7</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9636226</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Antibiot (Tokyo). 1998 May;51(5):487-91</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">9666177</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>EMBO J. 1994 Dec 15;13(24):5944-57</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">7529175</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
</PubmedData>
</pubmed>
<affiliations>
<list>
<country>
<li>États-Unis</li>
</country>
</list>
<tree>
<noCountry>
<name sortKey="Cardenas, M E" sort="Cardenas, M E" uniqKey="Cardenas M" first="M E" last="Cardenas">M E Cardenas</name>
<name sortKey="Cavallo, L M" sort="Cavallo, L M" uniqKey="Cavallo L" first="L M" last="Cavallo">L M Cavallo</name>
<name sortKey="Cox, G" sort="Cox, G" uniqKey="Cox G" first="G" last="Cox">G. Cox</name>
<name sortKey="Gorlach, J M" sort="Gorlach, J M" uniqKey="Gorlach J" first="J M" last="Görlach">J M Görlach</name>
<name sortKey="Heitman, J" sort="Heitman, J" uniqKey="Heitman J" first="J" last="Heitman">J. Heitman</name>
<name sortKey="Perfect, J R" sort="Perfect, J R" uniqKey="Perfect J" first="J R" last="Perfect">J R Perfect</name>
</noCountry>
<country name="États-Unis">
<noRegion>
<name sortKey="Cruz, M C" sort="Cruz, M C" uniqKey="Cruz M" first="M C" last="Cruz">M C Cruz</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Bois/explor/RapamycinFungusV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001A54 | SxmlIndent | more

Ou

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001A54 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Bois
   |area=    RapamycinFungusV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:10330150
   |texte=   Rapamycin antifungal action is mediated via conserved complexes with FKBP12 and TOR kinase homologs in Cryptococcus neoformans.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:10330150" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a RapamycinFungusV1 

Wicri

This area was generated with Dilib version V0.6.38.
Data generation: Thu Nov 19 21:55:41 2020. Site generation: Thu Nov 19 22:00:39 2020