Role of Sirtuin1-p53 regulatory axis in Aging, Cancer and Cellular Reprogramming.

Role of Sirtuin1-p53 regulatory axis in Aging, Cancer and Cellular Reprogramming. Ageing Res Rev. 2018 Feb 21;: Authors: Ong ALC, Ramasamy TS Abstract Regulatory role of Sirtuin 1 (SIRT1), one of the most extensively studied members of its kind in histone deacetylase family in governing multiple cellular fates, is predominantly linked to p53 activity. SIRT1 deacetylates p53 in a NAD+-dependent manner to inhibit transcription activity of p53, in turn modulate pathways that are implicated in regulation of tissue homoeostasis and many disease states. In this review, we discuss the role of SIRT1-p53 pathway and its regulatory axis in the cellular events which are implicated in cellular aging, cancer and reprogramming. It is noteworthy that these cellular events share few common regulatory pathways, including Sirt1-p53-LDHA-Myc,miR-34a,-Let7 regulatory network, which forms a positive feedback loop that controls cell cycle, metabolism, proliferation, differentiation, epigenetics and many others. In the context of aging, SIRT1 expression is reduced as a protective mechanism against oncogenesis and for maintenance of tissue homeostasis. Interestingly, its activation in aged cells is evidenced in response to DNA damage to protect the cells from p53-dependent apoptosis or senescence, predispose these cells to neoplastic transformation. Importantly, the dual roles of Sirt1-p53 axis in aging and tumourigenesis, either as tumour suppressor or tumour promoter are dete...
Source: Ageing Research Reviews - Category: Genetics & Stem Cells Authors: Tags: Ageing Res Rev Source Type: research

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