Regulation of the Cell Cycle and role of Ink4 Family in cancer
Regulation of the Cell Cycle and role of Ink4 Family in cancer
Samaneh Alijanian,1,*
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Introduction: The Ink4 family of proteins consists of four members: p15Ink4b, p18Ink4c, p19Ink4d, p16Ink4a, and p19Ink4d. The only D-type cyclin-dependent kinases that the Ink4 family of proteins bind to and block are CDK4 and CDK6. In co-immunoprecipitation tests, a protein that interacted with CDK4 and was later identified as MTS1 was determined to be the first member of the Ink4a family. This study's goal was to learn more about how the Ink4 Family affects cancer and how the cell cycle is regulated.
Methods: This study was the regulation of the cell cycle and role of the ink4 family in cancer from scientific databases such as science direct, springer, google scholar, and PubMed.
Results: Results have indicated the key structural similarities amongst ink4 proteins include the presence of four or five ankyrin repeats, which mediate protein-protein interactions with cdk4/6. each repetition consists of an extended strand joined to the following extended strand by a helix-loop-helix (hlh) motif. the p19ink4d-cdk6 complex's crystal structure has been determined, and this information has been extremely helpful in understanding how ink proteins block cdk. the p19ink4d ankyrin repeats form a "cap" over cdk6's n-terminal domain and cause it to migrate spatially away from the c terminus. while it prevents effective at binding, this event has little effect on CDK-cyclin complex formation. all four ink proteins have similar pharmacological actions toward cdk4 and cdk6, as would be predicted from their structural similarities. the ability of a short peptide generated from one of the ankyrin motifs to bind and inhibit cdk4 is intriguing and suggests the significance of these domains in ink4 functioning.
Conclusion: Ink proteins have comparable tertiary structures and similar biochemical activity, but their regulation is different. Most tissues do not express p16Ink4a. Instead, it is brought on by the production of transforming or oncogenic proteins as well as by cellular senescence. The expression of p16Ink4a is controlled by numerous oncogenes and tumor suppressors. For instance, p16Ink4a levels are elevated in primary rodent cells when Ras is overexpressed. The tumor suppressor p53 or the retinoblastoma susceptibility protein, Rb, can both be inactivated to increase p16Ink4a expression. TGF-, on the other hand, is one example of a growth-inhibitory factor (anti-mitogen) that controls p15Ink4b expression. Only the expression of p18Ink4c and p19Ink4d appears to be controlled throughout the cell cycle, peaking during the S phase. During development, Ink4 protein expression patterns are also variably controlled.