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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2010-5-5
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pubmed:abstractText |
The RhoA GTPase is crucial in numerous biological functions and is linked to cancer metastasis. However, the understanding of the molecular mechanism responsible for RhoA transcription is still very limited. Here we show that RhoA transcription is orchestrated by the Myc-Skp2-Miz1-p300 transcriptional complex. Skp2 cooperates with Myc to induce RhoA transcription by recruiting Miz1 and p300 to the RhoA promoter independently of Skp1-Cullin-F-box protein containing complex (SCF)-Skp2 E3 ligase activity. Deficiency of this complex results in impairment in RhoA expression, cell migration, invasion, and breast cancer metastasis, recapitulating the phenotypes observed in RhoA knockdown, and RhoA restoration rescues the defect in cell invasion. Overexpression of the Myc-Skp2-Miz1 complex is found in metastatic human cancers and is correlated with RhoA expression. Our study provides insight into how oncogenic Skp2 and Myc coordinate to induce RhoA transcription and establishes a novel SCF-Skp2 E3-ligase-independent function for oncogenic Skp2 in transcription and cancer metastasis.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/E1A-Associated p300 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Ep300 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Miz1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Multiprotein Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein p55(v-myc),
http://linkedlifedata.com/resource/pubmed/chemical/Protein Inhibitors of Activated STAT,
http://linkedlifedata.com/resource/pubmed/chemical/S-Phase Kinase-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SKP Cullin F-Box Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/rhoA GTP-Binding Protein
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1476-4679
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pubmed:author |
pubmed-author:ChanChia-HsinCH,
pubmed-author:HuangHsuan-YingHY,
pubmed-author:HungMien-ChieMC,
pubmed-author:KangHong-YoHY,
pubmed-author:LeeSzu-WeiSW,
pubmed-author:LiChien-FengCF,
pubmed-author:LinHui-KuanHK,
pubmed-author:NakayamaKeiichi IKI,
pubmed-author:PandolfiPier PaoloPP,
pubmed-author:WangJingJ,
pubmed-author:WuChing-YuanCY,
pubmed-author:WuJuanJ,
pubmed-author:YangWei-LeiWL
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pubmed:issnType |
Electronic
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
457-67
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pubmed:meshHeading |
pubmed-meshheading:20383141-Animals,
pubmed-meshheading:20383141-Cell Line,
pubmed-meshheading:20383141-E1A-Associated p300 Protein,
pubmed-meshheading:20383141-Humans,
pubmed-meshheading:20383141-Mice,
pubmed-meshheading:20383141-Mice, Knockout,
pubmed-meshheading:20383141-Multiprotein Complexes,
pubmed-meshheading:20383141-Neoplasm Metastasis,
pubmed-meshheading:20383141-Neoplasms,
pubmed-meshheading:20383141-Nuclear Proteins,
pubmed-meshheading:20383141-Oncogene Protein p55(v-myc),
pubmed-meshheading:20383141-Promoter Regions, Genetic,
pubmed-meshheading:20383141-Protein Inhibitors of Activated STAT,
pubmed-meshheading:20383141-S-Phase Kinase-Associated Proteins,
pubmed-meshheading:20383141-SKP Cullin F-Box Protein Ligases,
pubmed-meshheading:20383141-Transcription, Genetic,
pubmed-meshheading:20383141-Ubiquitin-Protein Ligases,
pubmed-meshheading:20383141-rhoA GTP-Binding Protein
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pubmed:year |
2010
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pubmed:articleTitle |
Deciphering the transcriptional complex critical for RhoA gene expression and cancer metastasis.
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pubmed:affiliation |
Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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