Dataset Information

Cross-talk between CDK4/6 and SMYD2 regulates gene transcription, tubulin methylation, and ciliogenesis.

ABSTRACT: Dysregulation of cyclin-dependent kinases 4 and 6 (CDK4/6) by unknown mechanisms is highly prevalent in human disease. In this study, we identify direct cross-talk between CDK4/6 and the epigenome via its previously unidentified substrate, SMYD2, a histone/lysine methyltransferase. CDK4/6 positively regulates the phosphorylation and enzymatic activity of SMYD2, while SMYD2 also positively regulates the expression of CDK4/6. We also identify SMYD2 as an ?-tubulin methyltransferase, thus connecting CDK4/6-SMYD2 signaling to microtubule dynamics. In addition, depletion or inhibition of CDK4/6 and SMYD2 resulted in increased cilia assembly by affecting (i) microtubule stability and (ii) the expression of IFT20, further connecting CDK4/6-SMYD2 to ciliogenesis. In clinical settings such as breast cancer and autosomal dominant polycystic kidney disease (ADPKD), targeting the up-regulated CDK4/6 and SMYD2 with inhibitors results in restoration of the primary cilium in tumor and cystic cells, which may normalize cilia-mediated extracellular signals that regulate growth, development, and cellular homeostasis.

SUBMITTER: Li LX

PROVIDER: S-EPMC7608814 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Cross-talk between CDK4/6 and SMYD2 regulates gene transcription, tubulin methylation, and ciliogenesis.

Li Linda Xiaoyan LX Zhou Julie Xia JX Wang Xiaodong X Zhang Hongbing H Harris Peter C PC Calvet James P JP Li Xiaogang X

Science advances 20201030 44

Dysregulation of cyclin-dependent kinases 4 and 6 (CDK4/6) by unknown mechanisms is highly prevalent in human disease. In this study, we identify direct cross-talk between CDK4/6 and the epigenome via its previously unidentified substrate, SMYD2, a histone/lysine methyltransferase. CDK4/6 positively regulates the phosphorylation and enzymatic activity of SMYD2, while SMYD2 also positively regulates the expression of CDK4/6. We also identify SMYD2 as an α-tubulin methyltransferase, thus connectin ...[more]

PMID: 33127671

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Dataset Information

Cross-talk between CDK4/6 and SMYD2 regulates gene transcription, tubulin methylation, and ciliogenesis.

Publications

Cross-talk between CDK4/6 and SMYD2 regulates gene transcription, tubulin methylation, and ciliogenesis.

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