| First Author | Li LX | Year | 2020 |
| Journal | Sci Adv | Volume | 6 |
| Issue | 44 | PubMed ID | 33127671 |
| Mgi Jnum | J:313066 | Mgi Id | MGI:6790736 |
| Doi | 10.1126/sciadv.abb3154 | Citation | Li LX, et al. (2020) Cross-talk between CDK4/6 and SMYD2 regulates gene transcription, tubulin methylation, and ciliogenesis. Sci Adv 6(44) |
| abstractText | 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 alpha-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. |
