| First Author | Li X | Year | 2018 |
| Journal | Stem Cell Reports | Volume | 10 |
| Issue | 2 | Pages | 339-346 |
| PubMed ID | 29307578 | Mgi Jnum | J:273928 |
| Mgi Id | MGI:6282867 | Doi | 10.1016/j.stemcr.2017.12.006 |
| Citation | Li X, et al. (2018) Cell-Cycle-Specific Function of p53 in Fanconi Anemia Hematopoietic Stem and Progenitor Cell Proliferation. Stem Cell Reports 10(2):339-346 |
| abstractText | 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 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. |
