What does p16 protein do?

p16 is a tumor suppressor protein that plays an important role in regulating the cell circle. As a CDK inhibitor, p16 can slow down the progression of the cell cycle by inactivating the CDK that phosphorylates the retinoblastoma protein, which is also a tumor suppressor protein that regulates the cell circle.

How is p16 activated?

It has been shown that p16 is induced by oncogenic RAS causing premature senescence to protect cells from hyperproliferation (8-10). The decrease of ANRIL expression might be required for p16 activation and induction of premature senescence.

What is p16 p21?

The tumor-suppressor proteins p53, p21, and p16 are major regulators of the G1/S cell–cycle checkpoint. Upon p53 stabilization, the transcription of p21 is induced, subsequently resulting in the inhibition of CDK4/6–cyclin D and CDK2–cyclin E complexes by p21.

Is p16 good or bad?

Expression of p16INK4A (p16 positive) is highly correlated with human papilloma virus (HPV) infection in head and neck squamous cell carcinoma (HNSCC), however, p16-positivity is not limited to HPV positive tumors and therefore, not a perfect surrogate for HPV.

Is p21 a protein?

Cyclin-dependent kinase inhibitor 1, also known as CDK-interacting protein 1, or more simply as p21, is a cell cycle inhibitor that promotes both CDK/cyclin inhibition as well as cell cycle arrest during the G1/S phase. In humans, p21 is encoded by the CDKN1A gene on chromosome six.

What is p53 and p16?

Abstract. p16INK4A and p53 are two major tumor suppressor proteins that are both upregulated in response to various cellular stresses and during senescence and aging.

What is negative p16?

Patients with p16 negative/HPV16 negative status had the worst survival for all sites combined as well as for OP. p16 status is an important prognostic indicator in both OPSCC and non-OPSCC and the p16 positive/HPV16 negative group is likely a distinct subgroup lacking any HPV genotype.

What does negative p16 mean?

Oropharyngeal (p16-) cancer staging refers to TNM staging of carcinomas originating in the oropharynx that are not human papillomavirus (HPV)-associated. This system most commonly pertains to squamous cell carcinomas that tested negative for p16, an immunohistochemical proxy for HPV infection, or were not tested.

Where is the p21 protein produced?

p21 represents a major target of p53 activity and thus is associated with linking DNA damage to cell cycle arrest. This protein is encoded by the CDKN1A gene located on chromosome 6 (6p21.

How are INK4 proteins related to CDK4 / 6?

The founding member of the Ink4a family was discovered as a protein that interacted with CDK4 in co-immunoprecipitation experiments, 16 subsequently identified as MTS1. Ink4 proteins are homologous in primary structure, sharing the presence of four or five ankyrin repeats, which are responsible for protein-protein interactions with CDK4/6.

What are the members of the INK4 family?

INK4 is a family of cyclin-dependent kinase inhibitors (CKIs). The members of this family ( p16 INK4a, p15 INK4b, p18 INK4c, p19 INK4d) are inhibitors of CDK4 (hence their name IN hibitors of CD K4 ), and of CDK6.

What are the exons of the INK4 gene?

It encodes yet another gene product, pAlt, consisting of p15Ink4b exon 1 joined to p16Ink4a exons 2 and 3 ( Tian et al., 2014 ). pAlt is induced during early contact inhibition and upon a variety of stresses, including UV irradiation]

How are the expression patterns of INK4 proteins regulated?

Only p18 Ink4c and p19 Ink4d expression seems to be regulated during various phases of the cell cycle, with expression peaking during S phase. 21 The expression patterns of Ink4 proteins are also differentially regulated during development. The structure of the genomic Ink4a locus is unique.