UBE4B: A Promising Regulatory Molecule in Neuronal Death and Survival
Identifieur interne : 000C45 ( Pmc/Curation ); précédent : 000C44; suivant : 000C46UBE4B: A Promising Regulatory Molecule in Neuronal Death and Survival
Auteurs : Rami Abou Zeinab ; Hong Wu ; Consolato Sergi ; Roger LengSource :
- International Journal of Molecular Sciences [ 1422-0067 ] ; 2012.
Abstract
Neuronal survival and death of neurons are considered a fundamental mechanism in the regulation of the nervous system during early development of the system and in adulthood. Defects in this mechanism are highly problematic and are associated with many neurodegenerative diseases. Because neuronal programmed death is apoptotic in nature, indicating that apoptosis is a key regulatory process, the p53 family members (p53, p73, p63) act as checkpoints in neurons due to their role in apoptosis. The complexity of this system is due to the existence of different naturally occurring isoforms that have different functions from the wild types (WT), varying from apoptotic to anti-apoptotic effects. In this review, we focus on the role of UBE4B (known as Ube4b or Ufd2a in mouse), an E3/E4 ligase that triggers substrate polyubiquitination, as a master regulatory ligase associated with the p53 family WT proteins and isoforms in regulating neuronal survival. UBE4B is also associated with other pathways independent of the p53 family, such as polyglutamine aggregation and Wallerian degeneration, both of which are critical in neurodegenerative diseases. Many of the hypotheses presented here are gateways to understanding the programmed death/survival of neurons regulated by UBE4B in normal physiology, and a means of introducing potential therapeutic approaches with implications in treating several neurodegenerative diseases.
Url:
DOI: 10.3390/ijms131216865
PubMed: 23222733
PubMed Central: 3546727
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">UBE4B: A Promising Regulatory Molecule in Neuronal Death and Survival</title><author><name sortKey="Zeinab, Rami Abou" sort="Zeinab, Rami Abou" uniqKey="Zeinab R" first="Rami Abou" last="Zeinab">Rami Abou Zeinab</name></author><author><name sortKey="Wu, Hong" sort="Wu, Hong" uniqKey="Wu H" first="Hong" last="Wu">Hong Wu</name></author><author><name sortKey="Sergi, Consolato" sort="Sergi, Consolato" uniqKey="Sergi C" first="Consolato" last="Sergi">Consolato Sergi</name></author><author><name sortKey="Leng, Roger" sort="Leng, Roger" uniqKey="Leng R" first="Roger" last="Leng">Roger Leng</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23222733</idno><idno type="pmc">3546727</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546727</idno><idno type="RBID">PMC:3546727</idno><idno type="doi">10.3390/ijms131216865</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000C45</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000C45</idno><idno type="wicri:Area/Pmc/Curation">000C45</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000C45</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">UBE4B: A Promising Regulatory Molecule in Neuronal Death and Survival</title><author><name sortKey="Zeinab, Rami Abou" sort="Zeinab, Rami Abou" uniqKey="Zeinab R" first="Rami Abou" last="Zeinab">Rami Abou Zeinab</name></author><author><name sortKey="Wu, Hong" sort="Wu, Hong" uniqKey="Wu H" first="Hong" last="Wu">Hong Wu</name></author><author><name sortKey="Sergi, Consolato" sort="Sergi, Consolato" uniqKey="Sergi C" first="Consolato" last="Sergi">Consolato Sergi</name></author><author><name sortKey="Leng, Roger" sort="Leng, Roger" uniqKey="Leng R" first="Roger" last="Leng">Roger Leng</name></author></analytic><series><title level="j">International Journal of Molecular Sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Neuronal survival and death of neurons are considered a fundamental mechanism in the regulation of the nervous system during early development of the system and in adulthood. Defects in this mechanism are highly problematic and are associated with many neurodegenerative diseases. Because neuronal programmed death is apoptotic in nature, indicating that apoptosis is a key regulatory process, the p53 family members (p53, p73, p63) act as checkpoints in neurons due to their role in apoptosis. The complexity of this system is due to the existence of different naturally occurring isoforms that have different functions from the wild types (WT), varying from apoptotic to anti-apoptotic effects. In this review, we focus on the role of UBE4B (known as Ube4b or Ufd2a in mouse), an E3/E4 ligase that triggers substrate polyubiquitination, as a master regulatory ligase associated with the p53 family WT proteins and isoforms in regulating neuronal survival. UBE4B is also associated with other pathways independent of the p53 family, such as polyglutamine aggregation and Wallerian degeneration, both of which are critical in neurodegenerative diseases. Many of the hypotheses presented here are gateways to understanding the programmed death/survival of neurons regulated by UBE4B in normal physiology, and a means of introducing potential therapeutic approaches with implications in treating several neurodegenerative diseases.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Yuan, J" uniqKey="Yuan J">J. Yuan</name></author><author><name sortKey="Yankner, B A" uniqKey="Yankner B">B.A. Yankner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jacobs, W B" uniqKey="Jacobs W">W.B. Jacobs</name></author><author><name sortKey="Kaplan, D R" uniqKey="Kaplan D">D.R. Kaplan</name></author><author><name sortKey="Miller, F D" uniqKey="Miller F">F.D. Miller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blaschke, A J" uniqKey="Blaschke A">A.J. Blaschke</name></author><author><name sortKey="Staley, K" uniqKey="Staley K">K. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Mol Sci</journal-id><journal-id journal-id-type="iso-abbrev">Int J Mol Sci</journal-id><journal-id journal-id-type="publisher-id">ijms</journal-id><journal-title-group><journal-title>International Journal of Molecular Sciences</journal-title></journal-title-group><issn pub-type="epub">1422-0067</issn><publisher><publisher-name>Molecular Diversity Preservation International (MDPI)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23222733</article-id><article-id pub-id-type="pmc">3546727</article-id><article-id pub-id-type="doi">10.3390/ijms131216865</article-id><article-id pub-id-type="publisher-id">ijms-13-16865</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>UBE4B: A Promising Regulatory Molecule in Neuronal Death and Survival</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zeinab</surname><given-names>Rami Abou</given-names></name></contrib><contrib contrib-type="author"><name><surname>Wu</surname><given-names>Hong</given-names></name></contrib><contrib contrib-type="author"><name><surname>Sergi</surname><given-names>Consolato</given-names></name></contrib><contrib contrib-type="author"><name><surname>Leng</surname><given-names>Roger</given-names></name><xref ref-type="corresp" rid="c1-ijms-13-16865">*</xref></contrib><aff id="af1-ijms-13-16865">Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2S2, Canada; E-Mails:<email>abouzein@ualberta.ca</email> (R.A.Z.);<email>hwu4@ualberta.ca</email> (H.W.);<email>sergi@ualberta.ca</email> (C.S.)</aff></contrib-group><author-notes><corresp id="c1-ijms-13-16865"><label>*</label>Author to whom correspondence should be addressed; E-Mail: <email>rleng@ualberta.ca</email>; Tel.: +1-780-492-4985; Fax: +1-780-492-9974.</corresp></author-notes><pub-date pub-type="collection"><year>2012</year></pub-date><pub-date pub-type="epub"><day>10</day><month>12</month><year>2012</year></pub-date><volume>13</volume><issue>12</issue><fpage>16865</fpage><lpage>16879</lpage><history><date date-type="received"><day>07</day><month>10</month><year>2012</year></date><date date-type="rev-recd"><day>22</day><month>11</month><year>2012</year></date><date date-type="accepted"><day>27</day><month>11</month><year>2012</year></date></history><permissions><copyright-statement>© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.</copyright-statement><copyright-year>2012</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0"><license-p><pmc-comment>CREATIVE COMMONS</pmc-comment>This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/3.0/">http://creativecommons.org/licenses/by/3.0/</ext-link>).</license-p></license></permissions><abstract><p>Neuronal survival and death of neurons are considered a fundamental mechanism in the regulation of the nervous system during early development of the system and in adulthood. Defects in this mechanism are highly problematic and are associated with many neurodegenerative diseases. Because neuronal programmed death is apoptotic in nature, indicating that apoptosis is a key regulatory process, the p53 family members (p53, p73, p63) act as checkpoints in neurons due to their role in apoptosis. The complexity of this system is due to the existence of different naturally occurring isoforms that have different functions from the wild types (WT), varying from apoptotic to anti-apoptotic effects. In this review, we focus on the role of UBE4B (known as Ube4b or Ufd2a in mouse), an E3/E4 ligase that triggers substrate polyubiquitination, as a master regulatory ligase associated with the p53 family WT proteins and isoforms in regulating neuronal survival. UBE4B is also associated with other pathways independent of the p53 family, such as polyglutamine aggregation and Wallerian degeneration, both of which are critical in neurodegenerative diseases. Many of the hypotheses presented here are gateways to understanding the programmed death/survival of neurons regulated by UBE4B in normal physiology, and a means of introducing potential therapeutic approaches with implications in treating several neurodegenerative diseases.</p></abstract><kwd-group><kwd>UBE4B</kwd><kwd>p53</kwd><kwd>p73</kwd><kwd>p63</kwd><kwd>nervous system</kwd><kwd>apoptosis</kwd><kwd>neurodegenerative diseases</kwd></kwd-group></article-meta></front><floats-group><fig id="f1-ijms-13-16865" position="float"><label>Figure 1</label><caption><p>Schematic model for UBE4B showing the inhibition (⊣), stabilization (→), or possible relation (?) with p53 family proteins, Wallerian pathway, and polyglutamination in neurodegenerative diseases.</p></caption><graphic xlink:href="ijms-13-16865f1"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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