Stem cells: The promises and perils of p53

Abstract

Five studies show that disabling p53, an essential tumour-suppressor protein, improves the efficiency of stem-cell production. Are these results a ‘heads up’ that cancer cells and stem cells are disturbingly similar?

Figure 1. Overlapping mechanisms control iPS-cell and cancer-cell production

Normal fibroblasts, which are mature, differentiated cells, can be reprogrammed into induced pluripotent stem (iPS) cells or tumour cells by a combination of defined factors. a, The transcription factors c-Myc and Klf4 promote reprogramming of fibroblasts into iPS cells in a manner that conceptually parallels their roles in transformng normal cells into tumour cells. Oct4 and Sox2, although overexpressed in cancers, are currently thought to function specifically to promote iPS-cell formation. b, Conversely, the p53 tumour-suppressor protein, which can be induced by p19^Arf, directly or indirectly limits the reprogramming of fibroblasts into iPS cells- or into transformed cancer cells by inducing apoptosis, or cellular senescence through its target protein, the cell-cycle inhibitor p21. Another cell-cycle inhibitor, p16^Ink4a, also promotes cellular senescence directly to limit both processes. The Ink4a/Arf locus (not shown), which encodes p19^Arf and p16^Ink4a, is silenced during iPS reprogramming,.