Overexpression of the fanconi anemia group C gene (FAC) protects hematopoietic progenitors from death induced by Fas-mediated apoptosis.
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.
Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland 20892, USA.
J
J
Wang
T
T
Otsuki
H
H
Youssoufian
J L
JL
Foe
S
S
Kim
M
M
Devetten
J
J
Yu
Y
Y
Li
D
D
Dunn
J M
JM
Liu
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D018797:Cell Cycle Proteins; D003114:Colony-Forming Units Assay; D004268:DNA-Binding Proteins; D005199:Fanconi Anemia / Q000235:genetics*; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; C505661:FASLG protein, human; C497652:Fancc protein, mouse; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D007371:Interferon-gamma