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Deciphering the transcriptional complex critical for RhoA gene expression and cancer metastasis.

ABSTRACT: 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.

SUBMITTER: Chan CH

PROVIDER: S-EPMC3855841 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Deciphering the transcriptional complex critical for RhoA gene expression and cancer metastasis.

Chan Chia-Hsin CH Lee Szu-Wei SW Li Chien-Feng CF Wang Jing J Yang Wei-Lei WL Wu Ching-Yuan CY Wu Juan J Nakayama Keiichi I KI Kang Hong-Yo HY Huang Hsuan-Ying HY Hung Mien-Chie MC Pandolfi Pier Paolo PP Lin Hui-Kuan HK

Nature cell biology 20100411 5

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 ac ...[more]

PMID: 20383141

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Dataset Information

Deciphering the transcriptional complex critical for RhoA gene expression and cancer metastasis.

Publications

Deciphering the transcriptional complex critical for RhoA gene expression and cancer metastasis.

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