A new role of NUAK1: directly phosphorylating p53 and regulating cell proliferation
It has been suggested that adenosine monophosphate-activated protein kinase (AMPK) and 12 AMPK-related kinases (ARK), including novel (nua) kinase family 1 (NUAK1), are activated by master kinase LKB1, a major tumor suppressor. Apart from evidence to suggest that NUAK1 participates in induction of t...
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| Veröffentlicht in: | Oncogene 2011-06, Vol.30 (26), p.2933-2942 |
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| creator | Hou, X Liu, J-E Liu, W Liu, C-Y Liu, Z-Y Sun, Z-Y |
| description | It has been suggested that adenosine monophosphate-activated protein kinase (AMPK) and 12 AMPK-related kinases (ARK), including novel (nua) kinase family 1 (NUAK1), are activated by master kinase LKB1, a major tumor suppressor. Apart from evidence to suggest that NUAK1 participates in induction of tumor survival, invasion and p53-independent cellular senescence, its detailed biological functions remain unclear. Here we showed that in the presence of wild-type LKB1, NUAK1 directly interacts with and phosphorylates p53
in vitro
and
in vivo
. The phosphorylation of p53 induced by LKB1 required the kinase activity of NUAK1 and phosphorylation of NUAK1 at Thr211 by LKB1 was essential for its kinase activity, which leads to the conclusion that LKB1 activates NUAK1 and regulates phosphorylation of p53 through the NUAK1 kinase, at least partially. LKB1/NUAK1 activation leads to cell cycle arrest at the G
1
/S border by inducing expression of p21/WAF1. Under the regulation of LKB1, NUAK1 interacts with p53 in the nucleus and binds to the p53-responsive element of p21/WAF1 promoter. These findings have highlighted a novel role for NUAK1 in LKB1-related signaling pathways; NUAK1 can regulate cell proliferation and exert tumor suppression through direct interaction with p53. |
| doi_str_mv | 10.1038/onc.2011.19 |
| format | Article |
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in vitro
and
in vivo
. The phosphorylation of p53 induced by LKB1 required the kinase activity of NUAK1 and phosphorylation of NUAK1 at Thr211 by LKB1 was essential for its kinase activity, which leads to the conclusion that LKB1 activates NUAK1 and regulates phosphorylation of p53 through the NUAK1 kinase, at least partially. LKB1/NUAK1 activation leads to cell cycle arrest at the G
1
/S border by inducing expression of p21/WAF1. Under the regulation of LKB1, NUAK1 interacts with p53 in the nucleus and binds to the p53-responsive element of p21/WAF1 promoter. These findings have highlighted a novel role for NUAK1 in LKB1-related signaling pathways; NUAK1 can regulate cell proliferation and exert tumor suppression through direct interaction with p53.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/onc.2011.19</identifier><identifier>PMID: 21317932</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/136/2091 ; 631/67/581 ; 631/80/86 ; Adenosine kinase ; AMP ; Apoptosis ; Biological and medical sciences ; Cell activation ; Cell Biology ; Cell cycle ; Cell Cycle - genetics ; Cell Cycle - physiology ; Cell growth ; Cell Nucleus - genetics ; Cell Nucleus - metabolism ; Cell physiology ; Cell Proliferation ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cells, Cultured ; Cyclin-dependent kinase inhibitor p21 ; Cyclin-Dependent Kinase Inhibitor p21 - genetics ; Cyclin-Dependent Kinase Inhibitor p21 - metabolism ; Cyclin-Dependent Kinase Inhibitor p21 - physiology ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Genes, Tumor Suppressor - physiology ; Genetic aspects ; HeLa Cells ; Human Genetics ; Humans ; Internal Medicine ; Kinases ; LKB1 protein ; Medicine ; Medicine & Public Health ; Molecular and cellular biology ; Neoplasms - genetics ; Neoplasms - metabolism ; Oncology ; original-article ; p53 Protein ; Phosphorylation ; Physiological aspects ; Promoter Regions, Genetic ; Protein Binding - physiology ; Protein kinase ; Protein Kinases - genetics ; Protein Kinases - metabolism ; Protein Kinases - physiology ; Regulatory sequences ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; Repressor Proteins - physiology ; Senescence ; Signal transduction ; Signal Transduction - genetics ; Signal Transduction - physiology ; Tumor proteins ; Tumor suppressor genes ; Tumor Suppressor Protein p53 - metabolism ; Tumors</subject><ispartof>Oncogene, 2011-06, Vol.30 (26), p.2933-2942</ispartof><rights>Macmillan Publishers Limited 2011</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2011 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2011.</rights><rights>Copyright Nature Publishing Group Jun 30, 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c612t-c09c7a7d0a37315815745c645c41fec911472a80bb668cd71fb51529dc644d903</citedby><cites>FETCH-LOGICAL-c612t-c09c7a7d0a37315815745c645c41fec911472a80bb668cd71fb51529dc644d903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/onc.2011.19$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/onc.2011.19$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24302785$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21317932$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hou, X</creatorcontrib><creatorcontrib>Liu, J-E</creatorcontrib><creatorcontrib>Liu, W</creatorcontrib><creatorcontrib>Liu, C-Y</creatorcontrib><creatorcontrib>Liu, Z-Y</creatorcontrib><creatorcontrib>Sun, Z-Y</creatorcontrib><title>A new role of NUAK1: directly phosphorylating p53 and regulating cell proliferation</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>It has been suggested that adenosine monophosphate-activated protein kinase (AMPK) and 12 AMPK-related kinases (ARK), including novel (nua) kinase family 1 (NUAK1), are activated by master kinase LKB1, a major tumor suppressor. Apart from evidence to suggest that NUAK1 participates in induction of tumor survival, invasion and p53-independent cellular senescence, its detailed biological functions remain unclear. Here we showed that in the presence of wild-type LKB1, NUAK1 directly interacts with and phosphorylates p53
in vitro
and
in vivo
. The phosphorylation of p53 induced by LKB1 required the kinase activity of NUAK1 and phosphorylation of NUAK1 at Thr211 by LKB1 was essential for its kinase activity, which leads to the conclusion that LKB1 activates NUAK1 and regulates phosphorylation of p53 through the NUAK1 kinase, at least partially. LKB1/NUAK1 activation leads to cell cycle arrest at the G
1
/S border by inducing expression of p21/WAF1. Under the regulation of LKB1, NUAK1 interacts with p53 in the nucleus and binds to the p53-responsive element of p21/WAF1 promoter. These findings have highlighted a novel role for NUAK1 in LKB1-related signaling pathways; NUAK1 can regulate cell proliferation and exert tumor suppression through direct interaction with p53.</description><subject>631/136/2091</subject><subject>631/67/581</subject><subject>631/80/86</subject><subject>Adenosine kinase</subject><subject>AMP</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Cell activation</subject><subject>Cell Biology</subject><subject>Cell cycle</subject><subject>Cell Cycle - genetics</subject><subject>Cell Cycle - physiology</subject><subject>Cell growth</subject><subject>Cell Nucleus - genetics</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell physiology</subject><subject>Cell Proliferation</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Cells, Cultured</subject><subject>Cyclin-dependent kinase inhibitor p21</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Genes, Tumor Suppressor - physiology</subject><subject>Genetic aspects</subject><subject>HeLa Cells</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Kinases</subject><subject>LKB1 protein</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular and cellular biology</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - metabolism</subject><subject>Oncology</subject><subject>original-article</subject><subject>p53 Protein</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Binding - physiology</subject><subject>Protein kinase</subject><subject>Protein Kinases - genetics</subject><subject>Protein Kinases - metabolism</subject><subject>Protein Kinases - physiology</subject><subject>Regulatory sequences</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - metabolism</subject><subject>Repressor Proteins - physiology</subject><subject>Senescence</subject><subject>Signal transduction</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - physiology</subject><subject>Tumor proteins</subject><subject>Tumor suppressor genes</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumors</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkk2LFDEQhoMo7uzqybsEZfGgPaby0el4Gxa_cNGD7jlk0umxl55kTLqR-fdWM-MuyoqEIlB5Uu9bRRHyBNgSmGhep-iXnAEswdwjC5C6rpQy8j5ZMKNYZbjgJ-S0lGvGmDaMPyQnHARoI_iCfF3RGH7SnIZAU0c_X60-wRva9jn4cdjT3fdUMPJ-cGMfN3SnBHWxpTlspmPKh2GgOyzQdyFjKsVH5EHnhhIeH-8zcvXu7beLD9Xll_cfL1aXla-Bj5VnxmunW-aEFqAaUFoqX2NI6II3gK1w17D1uq4b32ro1goUNy0ysjVMnJEXh7qo_mMKZbTbvsx2XAxpKrZpBJNCiOb_pJYS9WuO5LO_yOs05YhtIKRVLXBqCD3_F8RrCZJJjdO9oTZuCLaPXRqz87OwXfGaGSmUnK0t76DwtGHb-xRD12P-jw8vDx98TqXk0Nld7rcu7y0wOy-ExYWw80JYmE08PVqd1tvQ3rC_NwCB8yPgindDl130fbnlpGBcNwq5Vweu4FPchHzb8126vwA0oMcL</recordid><startdate>20110630</startdate><enddate>20110630</enddate><creator>Hou, X</creator><creator>Liu, J-E</creator><creator>Liu, W</creator><creator>Liu, C-Y</creator><creator>Liu, Z-Y</creator><creator>Sun, Z-Y</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20110630</creationdate><title>A new role of NUAK1: directly phosphorylating p53 and regulating cell proliferation</title><author>Hou, X ; Liu, J-E ; Liu, W ; Liu, C-Y ; Liu, Z-Y ; Sun, Z-Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c612t-c09c7a7d0a37315815745c645c41fec911472a80bb668cd71fb51529dc644d903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>631/136/2091</topic><topic>631/67/581</topic><topic>631/80/86</topic><topic>Adenosine kinase</topic><topic>AMP</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Cell activation</topic><topic>Cell Biology</topic><topic>Cell cycle</topic><topic>Cell Cycle - genetics</topic><topic>Cell Cycle - physiology</topic><topic>Cell growth</topic><topic>Cell Nucleus - genetics</topic><topic>Cell Nucleus - metabolism</topic><topic>Cell physiology</topic><topic>Cell Proliferation</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Cells, Cultured</topic><topic>Cyclin-dependent kinase inhibitor p21</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - metabolism</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene expression</topic><topic>Genes, Tumor Suppressor - physiology</topic><topic>Genetic aspects</topic><topic>HeLa Cells</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Kinases</topic><topic>LKB1 protein</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular and cellular biology</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - metabolism</topic><topic>Oncology</topic><topic>original-article</topic><topic>p53 Protein</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Binding - physiology</topic><topic>Protein kinase</topic><topic>Protein Kinases - genetics</topic><topic>Protein Kinases - metabolism</topic><topic>Protein Kinases - physiology</topic><topic>Regulatory sequences</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - metabolism</topic><topic>Repressor Proteins - physiology</topic><topic>Senescence</topic><topic>Signal transduction</topic><topic>Signal Transduction - genetics</topic><topic>Signal Transduction - physiology</topic><topic>Tumor proteins</topic><topic>Tumor suppressor genes</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hou, X</creatorcontrib><creatorcontrib>Liu, J-E</creatorcontrib><creatorcontrib>Liu, W</creatorcontrib><creatorcontrib>Liu, C-Y</creatorcontrib><creatorcontrib>Liu, Z-Y</creatorcontrib><creatorcontrib>Sun, Z-Y</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest research library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hou, X</au><au>Liu, J-E</au><au>Liu, W</au><au>Liu, C-Y</au><au>Liu, Z-Y</au><au>Sun, Z-Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A new role of NUAK1: directly phosphorylating p53 and regulating cell proliferation</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2011-06-30</date><risdate>2011</risdate><volume>30</volume><issue>26</issue><spage>2933</spage><epage>2942</epage><pages>2933-2942</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>It has been suggested that adenosine monophosphate-activated protein kinase (AMPK) and 12 AMPK-related kinases (ARK), including novel (nua) kinase family 1 (NUAK1), are activated by master kinase LKB1, a major tumor suppressor. Apart from evidence to suggest that NUAK1 participates in induction of tumor survival, invasion and p53-independent cellular senescence, its detailed biological functions remain unclear. Here we showed that in the presence of wild-type LKB1, NUAK1 directly interacts with and phosphorylates p53
in vitro
and
in vivo
. The phosphorylation of p53 induced by LKB1 required the kinase activity of NUAK1 and phosphorylation of NUAK1 at Thr211 by LKB1 was essential for its kinase activity, which leads to the conclusion that LKB1 activates NUAK1 and regulates phosphorylation of p53 through the NUAK1 kinase, at least partially. LKB1/NUAK1 activation leads to cell cycle arrest at the G
1
/S border by inducing expression of p21/WAF1. Under the regulation of LKB1, NUAK1 interacts with p53 in the nucleus and binds to the p53-responsive element of p21/WAF1 promoter. These findings have highlighted a novel role for NUAK1 in LKB1-related signaling pathways; NUAK1 can regulate cell proliferation and exert tumor suppression through direct interaction with p53.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>21317932</pmid><doi>10.1038/onc.2011.19</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/136/2091 631/67/581 631/80/86 Adenosine kinase AMP Apoptosis Biological and medical sciences Cell activation Cell Biology Cell cycle Cell Cycle - genetics Cell Cycle - physiology Cell growth Cell Nucleus - genetics Cell Nucleus - metabolism Cell physiology Cell Proliferation Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cells, Cultured Cyclin-dependent kinase inhibitor p21 Cyclin-Dependent Kinase Inhibitor p21 - genetics Cyclin-Dependent Kinase Inhibitor p21 - metabolism Cyclin-Dependent Kinase Inhibitor p21 - physiology Fundamental and applied biological sciences. Psychology Gene expression Genes, Tumor Suppressor - physiology Genetic aspects HeLa Cells Human Genetics Humans Internal Medicine Kinases LKB1 protein Medicine Medicine & Public Health Molecular and cellular biology Neoplasms - genetics Neoplasms - metabolism Oncology original-article p53 Protein Phosphorylation Physiological aspects Promoter Regions, Genetic Protein Binding - physiology Protein kinase Protein Kinases - genetics Protein Kinases - metabolism Protein Kinases - physiology Regulatory sequences Repressor Proteins - genetics Repressor Proteins - metabolism Repressor Proteins - physiology Senescence Signal transduction Signal Transduction - genetics Signal Transduction - physiology Tumor proteins Tumor suppressor genes Tumor Suppressor Protein p53 - metabolism Tumors |
| title | A new role of NUAK1: directly phosphorylating p53 and regulating cell proliferation |
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