School of Pharmacy
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 p53515C 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 plays a compensatory role in preventing FA HSCs from replicative exhaustion and suggest a cautious approach to manipulating p53 signaling as a therapeutic utility in FA.
Digital Commons Citation
Li, Xiaoli; Wilson, Andrew F.; Du, Wei; and Pang, Qishen, "Cell-Cycle-Specific Function of p53 in Fanconi Anemia Hematopoietic Stem and Progenitor Cell Proliferation" (2018). Clinical and Translational Science Institute. 775.
Li X, Wilson AF, Du W, Pang Q. Cell-Cycle-Specific Function of p53 in Fanconi Anemia Hematopoietic Stem and Progenitor Cell Proliferation. Stem Cell Reports. 2018;10(2):339-346. doi:10.1016/j.stemcr.2017.12.006