Regulation of p16INK4A, The Cyclin Dependent Kinase Inhibitor & the Tumor Suppressor

Abstract

p16INK4A is a tumor suppressor protein which inhibits the activities of CDK4 and CDK6 thus leading cell cycle arrest in G1 phase. Therefore, regulation of p16INK4A levels and activity play a crucial role in maintenance of homeostasis. Since p16INK4A has key roles in important cellular physiological processes such as tumor suppression, senescence, apoptosis, it must be tightly regulated. Here, I focus on how p16INK4A is regulated. Most of the literature is focused on the transcriptional regulation of p16INK4A therefore I include transcription factors or DNA binding proteins which lead to either repression or induction of p16INK4A gene. In the following part, post-transcriptional regulation of p16INK4A with RNA binding proteins and miRNAs are discussed. Last but not least the protein modifications of p16INK4A such as phosphorylation and ubiquitination are discussed. This review presents an extensive discussion on regulation of p16INK4A tumor suppressor protein.