Cell-Cycle-Specific Function of p53 in Fanconi Anemia Hematopoietic Stem and Progenitor Cell Proliferation.

ABSTRACT: Overactive p53 has been proposed as an important pathophysiological factor for bone marrow failure syndromes, including Fanconi anemia (FA). Here, we report a p53-dependent effect on hematopoietic stem and progenitor cell (HSPC) proliferation in mice deficient for the FA gene Fanca. Deletion of p53 in Fanca^-/- mice leads to replicative exhaustion of the hematopoietic stem cell (HSC) in transplant recipients. Using Fanca^-/- HSCs expressing the separation-of-function mutant p53^515C transgene, which selectively impairs the p53 function in apoptosis but keeps its cell-cycle checkpoint activities intact, we show that the p53 cell-cycle function is specifically required for the regulation of Fanca^-/- HSC proliferation. Our results demonstrate that p53

SUBMITTER: Li X 

PROVIDER: S-EPMC5830889 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature