P16ink4a Case Study

p16ink4a (also called Cdkn2a) is one of cancers and aging biomarkers involved in regulating cell cycle which is suppressed in early embryogenesis and progressively induced during ageing. At the present study, to investigate the evolutionary relationship of p16ink4a in human respect to other organisms, clustalx, GENEDOC and Tree view softwares and for investigation of gene network and various promoter elements of p16ink4a gene, genemania and Gene2promoter sorfwares were used, respectively. Regarding phylogenetic tree obtained from analysis of p16ink4a nucleotide sequence, Homo sapiens has the highest and lowest similarity to Chlorocebus sabaeus and Balaenoptera acutorostrata, respectively and altogether, sequence analysis of this gene showed
Emerging evidence from mouse models to study a key effector of p16Ink4a in establishing the senescent state [4] as potent protector from the main ageing-associated pathologies, including cardiovascular disorders, neurodegenerative diseases, diabetes, immune decay and cancer types. The recent studies in both humans and nonhuman models it has been appreciated that senescent cells alteration of metabolism (cell-autonomous alterations and changes at level of intercellular communication) as can be it endocrine, neuroendocrine, or neuronal [3]. Family members of cyclin-dependent kinase (CDK) inhibitor proteins (CDIs), which inactivate CDKs by cyclin/CDK complexes, has been isolated. Cylins, CDKs and CDIs are known as regulator of the progression of cell cycle in mammalian cells [5]. This family includes the p16INK4a, p21CIP1, p27KIP1 (associated proteins p15INK4b, p18INK4c, p19INK4d, and p57KIP2) [6] that contributes potentially as tumor suppressors and their inactivation in accordance with human carcinogenesis
Biochemical analyses so far have indicated that p16INK4A may activation by regulating Rb, and p19ARF by activating p53 through an interaction with the MDM2 protein[11]. Antisense noncoding RNA in the INK4 locus (ANRIL), as fourth INK4/ARF transcript, transcribed by RNA polymerase II [12] from the Chr9p21 locus. ANRIL spliced into multiple linear isoforms (Figure 1) [13] to regulate the vicinity of tumor suppressors three genes, CDKN2A, CDKN2B, and methyl-thioadenosine phosphorylase (MTAP), as well as is proposed to function as an epigenetic mechanisms regulator of INK4/ARF gene transcription, thereby regulate cell proliferation and