The cyclin-dependent kinase inhibitor p16INK4a physically interacts with transcription factor Sp1 and cyclin-dependent kinase 4 to transactivate microRNA-141 and microRNA-146b-5p spontaneously and in response to ultraviolet light-induced DNA damage.

ABSTRACT: p16(INK4a) is a tumor suppressor protein involved in several stress-related cellular responses, including apoptosis. Recent lines of evidence indicate that p16(INK4a) is also a modulator of gene expression. However, the molecular mechanisms underlying this novel function are still obscure. Here, we present clear evidence that p16(INK4a) modulates the levels of various microRNAs, with marked positive effect on miR-141 and miR-146b-5p. This effect is mediated through the formation of the p16-CDK4-Sp1 heterocomplex, which binds to Sp1 consensus-binding motifs present in the promoters of miR-141 and miR-146b-5p, and it enables their transcription. In addition, we have shown that p16(INK4a) interacts with Sp1 through the fourth ankyrin repeat, which is crucial for Sp1 binding to the miR-141 and

SUBMITTER: Al-Khalaf HH 

PROVIDER: S-EPMC3853297 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature