| First Author | Bellutti F | Year | 2018 |
| Journal | Cancer Discov | Volume | 8 |
| Issue | 7 | Pages | 884-897 |
| PubMed ID | 29899063 | Mgi Jnum | J:263926 |
| Mgi Id | MGI:6187748 | Doi | 10.1158/2159-8290.CD-17-0912 |
| Citation | Bellutti F, et al. (2018) CDK6 Antagonizes p53-Induced Responses during Tumorigenesis. Cancer Discov 8(7):884-897 |
| abstractText | Tumor formation is a multistep process during which cells acquire genetic and epigenetic changes until they reach a fully transformed state. We show that CDK6 contributes to tumor formation by regulating transcriptional responses in a stage-specific manner. In early stages, the CDK6 kinase induces a complex transcriptional program to block p53 in hematopoietic cells. Cells lacking CDK6 kinase function are required to mutate TP53 (encoding p53) to achieve a fully transformed immortalized state. CDK6 binds to the promoters of genes including the p53 antagonists Prmt5, Ppm1d, and Mdm4 The findings are relevant to human patients: Tumors with low levels of CDK6 have mutations in TP53 significantly more often than expected.Significance: CDK6 acts at the interface of p53 and RB by driving cell-cycle progression and antagonizing stress responses. While sensitizing cells to p53-induced cell death, specific inhibition of CDK6 kinase activity may provoke the outgrowth of p53-mutant clones from premalignant cells. Cancer Discov; 8(7); 884-97. (c)2018 AACR.This article is highlighted in the In This Issue feature, p. 781. |
