Overexpression of the fanconi anemia group C gene (FAC) protects hematopoietic progenitors from death induced by Fas-mediated apoptosis
Wang, J.; Otsuki, T.; Youssoufian, H.; Foe, J.L.; Kim, S.; Devetten, M.; Yu, J.; Li, Y.; Dunn, D.; Liu, J.M.
Cancer Research 58(16): 3538-3541
1998
ISSN/ISBN: 0008-5472 PMID: 9721856 Document Number: 497928
Fanconi anemia is a rare, inherited disorder characterized by bone marrow failure, congenital malformations, and cancer susceptibility. The group C Fanconi anemia gene, FAC, identified by expression cloning methods, encodes a protein of unknown function that may be involved in the response to apoptotic stimuli. Hematopoietic progenitor cells from Fac knock-out mice are hypersensitive to IFN-gamma, a molecule that can induce apoptosis through up-regulation of the Fas death receptor. In this study, we used FAC-overexpressing transgenic mice to examine the relationship between FAC and Fas-triggered cell death. Hematopoietic progenitors from FAC-transgenic mice were up to 10-fold less sensitive to the cytolytic effect of Fas-ligation. Our experiments implicate FAC in the regulation of apoptosis mediated by the Fas death receptor.