S6 Kinase 2 Is Bound to Chromatin‐Nuclear Matrix Cellular Fractions and Is Able to Phosphorylate Histone H3 at Threonine 45 In Vitro and In Vivo
Identifieur interne : 000F84 ( Main/Exploration ); précédent : 000F83; suivant : 000F85S6 Kinase 2 Is Bound to Chromatin‐Nuclear Matrix Cellular Fractions and Is Able to Phosphorylate Histone H3 at Threonine 45 In Vitro and In Vivo
Auteurs : Heba M. S. Ismail [Royaume-Uni, Égypte] ; Paul J. Hurd [Royaume-Uni] ; Mahmoud I. M. Khalil [Royaume-Uni] ; Tony Kouzarides [Royaume-Uni] ; Andrew Bannister [Royaume-Uni] ; Ivan Gout [Royaume-Uni]Source :
- Journal of Cellular Biochemistry [ 0730-2312 ] ; 2014-06.
Abstract
The activity of S6 kinases (S6K) is highly induced in cancer cells highlighting an essential role in carcinogenesis. The S6K family has two members: S6K1 and S6K2 which bear common as well as distinct features. In an attempt to identify S6K2 unique sequence features compared to S6K1, we applied extensive bioinformatic analysis and motif search approaches. Interestingly, we identified 14 unique protein signatures which are present in proteins directly connected to chromatin and/or involved in transcription regulation. Using chromatin binding assay, we biochemically showed that S6K2 is bound to chromatin as well as nuclear matrix cellular fractions in HEK293 cells. The presence of S6K2 in chromatin fractions raised the possibility that it may be in close proximity to a number of chromatin substrates. For that, we then searched for S6K phosphorylation consensus sites RXRXXT/S in mammalian proteins using the SWISS‐PROT database. Interestingly, we identified some potential phosphorylation sites in histone H3 (Thr45). Using in vitro kinase assays and siRNA‐based knockdown strategy; we confirmed that S6K2 but not S6K1 or AKT is essential for histone H3‐Thr45 phosphorylation in HEK293 cells. Furthermore, we show that the nuclear localisation sequence in the S6K2 C‐terminus is essential for this modification. We have found that, H3‐Thr45 phosphorylation correlates to S6K activation in response to mitogens and TPA‐induced cell differentiation of leukaemic cell lines U937, HL60 and THP1. Overall, we demonstrate that S6K2 is a novel kinase that can phosphorylate histone H3 at position Thr45, which may play a role during cell proliferation and/or differentiation. J. Cell. Biochem. 115: 1048–1062, 2014. © 2013 Wiley Periodicals, Inc.
Url:
DOI: 10.1002/jcb.24566
Affiliations:
- Royaume-Uni, Égypte
- Angleterre, Angleterre de l'Est, Grand Londres
- Cambridge, Londres
- University College de Londres, Université de Cambridge
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 001602
- to stream Istex, to step Curation: 001529
- to stream Istex, to step Checkpoint: 000211
- to stream Main, to step Merge: 000F85
- to stream Main, to step Curation: 000F84
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">S6 Kinase 2 Is Bound to Chromatin‐Nuclear Matrix Cellular Fractions and Is Able to Phosphorylate Histone H3 at Threonine 45 In Vitro and In Vivo</title><author><name sortKey="Ismail, Heba M S" sort="Ismail, Heba M S" uniqKey="Ismail H" first="Heba M. S." last="Ismail">Heba M. S. Ismail</name></author><author><name sortKey="Hurd, Paul J" sort="Hurd, Paul J" uniqKey="Hurd P" first="Paul J." last="Hurd">Paul J. Hurd</name></author><author><name sortKey="Khalil, Mahmoud I M" sort="Khalil, Mahmoud I M" uniqKey="Khalil M" first="Mahmoud I. M." last="Khalil">Mahmoud I. M. Khalil</name></author><author><name sortKey="Kouzarides, Tony" sort="Kouzarides, Tony" uniqKey="Kouzarides T" first="Tony" last="Kouzarides">Tony Kouzarides</name></author><author><name sortKey="Bannister, Andrew" sort="Bannister, Andrew" uniqKey="Bannister A" first="Andrew" last="Bannister">Andrew Bannister</name></author><author><name sortKey="Gout, Ivan" sort="Gout, Ivan" uniqKey="Gout I" first="Ivan" last="Gout">Ivan Gout</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:3C3B4526F32BAA015F09EB61062DFCAFEAA30A98</idno><date when="2014" year="2014">2014</date><idno type="doi">10.1002/jcb.24566</idno><idno type="url">https://api.istex.fr/ark:/67375/WNG-51X82PGN-5/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">001602</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001602</idno><idno type="wicri:Area/Istex/Curation">001529</idno><idno type="wicri:Area/Istex/Checkpoint">000211</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000211</idno><idno type="wicri:doubleKey">0730-2312:2014:Ismail H:s:kinase:is</idno><idno type="wicri:Area/Main/Merge">000F85</idno><idno type="wicri:Area/Main/Curation">000F84</idno><idno type="wicri:Area/Main/Exploration">000F84</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">S6 Kinase 2 Is Bound to Chromatin‐Nuclear Matrix Cellular Fractions and Is Able to Phosphorylate Histone H3 at Threonine 45 In Vitro and In Vivo</title><author><name sortKey="Ismail, Heba M S" sort="Ismail, Heba M S" uniqKey="Ismail H" first="Heba M. S." last="Ismail">Heba M. S. Ismail</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Structural and Molecular Biology, University College London, WC1E 6BT, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">University College de Londres</orgName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Égypte</country><wicri:regionArea>Cancer Biology Department, National Cancer Institute, Cairo University, Cairo</wicri:regionArea><wicri:noRegion>Cairo</wicri:noRegion></affiliation></author><author><name sortKey="Hurd, Paul J" sort="Hurd, Paul J" uniqKey="Hurd P" first="Paul J." last="Hurd">Paul J. Hurd</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Gurdon Institute and Department of Pathology, University of Cambridge, Cambridge</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation><affiliation wicri:level="3"><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><wicri:orgArea>School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, United Kingdom, E1 4NS</wicri:orgArea></affiliation></author><author><name sortKey="Khalil, Mahmoud I M" sort="Khalil, Mahmoud I M" uniqKey="Khalil M" first="Mahmoud I. M." last="Khalil">Mahmoud I. M. Khalil</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Structural and Molecular Biology, University College London, WC1E 6BT, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">University College de Londres</orgName></affiliation><affiliation></affiliation></author><author><name sortKey="Kouzarides, Tony" sort="Kouzarides, Tony" uniqKey="Kouzarides T" first="Tony" last="Kouzarides">Tony Kouzarides</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Gurdon Institute and Department of Pathology, University of Cambridge, Cambridge</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation></author><author><name sortKey="Bannister, Andrew" sort="Bannister, Andrew" uniqKey="Bannister A" first="Andrew" last="Bannister">Andrew Bannister</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Gurdon Institute and Department of Pathology, University of Cambridge, Cambridge</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation></author><author><name sortKey="Gout, Ivan" sort="Gout, Ivan" uniqKey="Gout I" first="Ivan" last="Gout">Ivan Gout</name><affiliation wicri:level="4"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Structural and Molecular Biology, University College London, WC1E 6BT, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName><orgName type="university">University College de Londres</orgName></affiliation><affiliation wicri:level="4"><orgName type="university">University College de Londres</orgName><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Royaume-Uni</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Cellular Biochemistry</title><title level="j" type="alt">JOURNAL OF CELLULAR BIOCHEMISTRY</title><idno type="ISSN">0730-2312</idno><idno type="eISSN">1097-4644</idno><imprint><biblScope unit="vol">115</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="1048">1048</biblScope><biblScope unit="page" to="1062">1062</biblScope><biblScope unit="page-count">15</biblScope><date type="published" when="2014-06">2014-06</date></imprint><idno type="ISSN">0730-2312</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0730-2312</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The activity of S6 kinases (S6K) is highly induced in cancer cells highlighting an essential role in carcinogenesis. The S6K family has two members: S6K1 and S6K2 which bear common as well as distinct features. In an attempt to identify S6K2 unique sequence features compared to S6K1, we applied extensive bioinformatic analysis and motif search approaches. Interestingly, we identified 14 unique protein signatures which are present in proteins directly connected to chromatin and/or involved in transcription regulation. Using chromatin binding assay, we biochemically showed that S6K2 is bound to chromatin as well as nuclear matrix cellular fractions in HEK293 cells. The presence of S6K2 in chromatin fractions raised the possibility that it may be in close proximity to a number of chromatin substrates. For that, we then searched for S6K phosphorylation consensus sites RXRXXT/S in mammalian proteins using the SWISS‐PROT database. Interestingly, we identified some potential phosphorylation sites in histone H3 (Thr45). Using in vitro kinase assays and siRNA‐based knockdown strategy; we confirmed that S6K2 but not S6K1 or AKT is essential for histone H3‐Thr45 phosphorylation in HEK293 cells. Furthermore, we show that the nuclear localisation sequence in the S6K2 C‐terminus is essential for this modification. We have found that, H3‐Thr45 phosphorylation correlates to S6K activation in response to mitogens and TPA‐induced cell differentiation of leukaemic cell lines U937, HL60 and THP1. Overall, we demonstrate that S6K2 is a novel kinase that can phosphorylate histone H3 at position Thr45, which may play a role during cell proliferation and/or differentiation. J. Cell. Biochem. 115: 1048–1062, 2014. © 2013 Wiley Periodicals, Inc.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li><li>Égypte</li></country><region><li>Angleterre</li><li>Angleterre de l'Est</li><li>Grand Londres</li></region><settlement><li>Cambridge</li><li>Londres</li></settlement><orgName><li>University College de Londres</li><li>Université de Cambridge</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Ismail, Heba M S" sort="Ismail, Heba M S" uniqKey="Ismail H" first="Heba M. S." last="Ismail">Heba M. S. Ismail</name></region><name sortKey="Bannister, Andrew" sort="Bannister, Andrew" uniqKey="Bannister A" first="Andrew" last="Bannister">Andrew Bannister</name><name sortKey="Gout, Ivan" sort="Gout, Ivan" uniqKey="Gout I" first="Ivan" last="Gout">Ivan Gout</name><name sortKey="Gout, Ivan" sort="Gout, Ivan" uniqKey="Gout I" first="Ivan" last="Gout">Ivan Gout</name><name sortKey="Gout, Ivan" sort="Gout, Ivan" uniqKey="Gout I" first="Ivan" last="Gout">Ivan Gout</name><name sortKey="Hurd, Paul J" sort="Hurd, Paul J" uniqKey="Hurd P" first="Paul J." last="Hurd">Paul J. Hurd</name><name sortKey="Hurd, Paul J" sort="Hurd, Paul J" uniqKey="Hurd P" first="Paul J." last="Hurd">Paul J. Hurd</name><name sortKey="Khalil, Mahmoud I M" sort="Khalil, Mahmoud I M" uniqKey="Khalil M" first="Mahmoud I. M." last="Khalil">Mahmoud I. M. Khalil</name><name sortKey="Kouzarides, Tony" sort="Kouzarides, Tony" uniqKey="Kouzarides T" first="Tony" last="Kouzarides">Tony Kouzarides</name></country><country name="Égypte"><noRegion><name sortKey="Ismail, Heba M S" sort="Ismail, Heba M S" uniqKey="Ismail H" first="Heba M. S." last="Ismail">Heba M. S. Ismail</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/StressCovidV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000F84 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000F84 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= StressCovidV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:3C3B4526F32BAA015F09EB61062DFCAFEAA30A98
|texte= S6 Kinase 2 Is Bound to Chromatin‐Nuclear Matrix Cellular Fractions and Is Able to Phosphorylate Histone H3 at Threonine 45 In Vitro and In Vivo
}}
| This area was generated with Dilib version V0.6.33. |  |