Regulation of Normal Somatic Cell and Cancer Cell Reprogramming by p53

Jie Yuan
2015 International Journal of Stem cell Research & Therapy  
Differentiated somatic cells have been reprogrammed to a pluripotent state by forced expression of a set of transcription factors [1] , indicating that terminally differentiated cells can be induced to undergo cell fate change. p53 reduces cancer initiation by regulating apoptosis, DNA repair, cell cycle and senescence, contributing to its main role as the "guardian of the genome". Recent studies show new roles of p53 in a wide range of processes, including cell self-renewal, differentiation,
more » ... d cell fate decisions [9] [10] [11] . Several lines of evidence suggested that p53 governs the quantity and quality of various stem cells through regulation of self renewal ability and differentiation. One example is that the p53 protein can be phosphorylated and suppress the transcription of Nanog, leading to stem cells to lose self renewal potential and then differentiation [12] . Many groups reported that p53 has been shown to inhibit reprogramming of fibroblasts to iPS cells [7, 8, [13] [14] [15] [16] [17]. Yamanaka et al. found that c-Myc induces p53-dependent apoptosis in fibroblasts, leading to a reduced rate of reprogramming [16] . Zhao et al. showed that depletion of p53 combined with overexpression of Utf1 dramatically increased in iPS cell formation [17]. Other groups also provided strong evidence that p53 serves as a potent barrier to somatic cell reprogramming and dramatically reduces the efficiency of dedifferentiation [12] [13] [14] . Mechanistically, the overexpression of exogenous transcription factors is thought to activate p53, which might in turn lead to cell cycle arrest and apoptosis. In addition, during pluripotency induction, Abstract Reprogramming healthy somatic cells into disease-relevant cell types through cellular reprogramming has been intensively investigated. The discovery of reprogramming methods holds the promise of generating desired cells for disease modeling, drug screening studies and treatment of numerous diseases. Recently studies also focus on different disease cell reprogramming, including cancer cell reprogramming. Reprogramming and tumorigenesis share many similarities and the tumor suppressor p53 suppresses both processes. Understanding of the roles of p53 in somatic cell and cancer cell reprogramming could illuminate molecular mechanisms underlying the pathogenesis of human cancer and develop novel strategies for cell replacement therapy and cancer treatment.
doi:10.23937/2469-570x/1410016 fatcat:iajqe4xaozhffbukkn577pzjoa