MZF1 mediates oncogene-induced senescence by promoting the transcription of p16^INK4A.

ABSTRACT: Oncogene induced senescence is a tumor suppressing defense mechanism, in which the cell cycle-dependent protein kinase (CDK) inhibitor p16^INK4A (encoded by the CDKN2A gene) plays a key role. We previously reported that a transcriptional co-activator chromodomain helicase DNA binding protein 7 (CHD7) mediates oncogenic ras-induced senescence by inducing transcription of the p16^INK4A gene. In the current study, we identified myeloid zinc finger 1 (MZF1) as the transcriptional factor that recruits CHD7 to the p16^INK4A promoter, where it mediates oncogenic ras-induced p16^INK4A transcription and senescence through CHD7, in primary human cells from multiple origins. Moreover, the expression of MZF1 is induced by oncogenic ras in senescent cells through

SUBMITTER: Wu D 

PROVIDER: S-EPMC8758531 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature