Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1

The Fanconi anemia group C protein (FANCC) plays an important role in hemat opoiesis by ensuring the survival of hematopoietic progenitor cells through an unknown mechanism. We investigated the function of FANCC by identifying FANCC-binding proteins in hematopoietic cells. Here we show that glutathio ne S-transferase P1-1 (GSTP1) interacts with FANCC, and that overexpression of both proteins in a myeloid progenitor cell line prevents apoptosis foll owing factor deprivation. FANCC increases GSTP1 activity after the inductio n of apoptosis. GSTP1 is an enzyme that catalyzes the detoxification of xen obiotics and by-products of oxidative stress, and it is frequently upregula ted in neoplastic cells. Although FANCC lacks homology with conventional di sulfide reductases, it functions by preventing the formation of inactivatin g disulfide bonds within GSTP1 during apoptosis. The prevention of protein oxidation by FANCC reveals a novel mechanism of enzyme regulation during ap optosis and has implications for the treatment of degenerative diseases wit h thiol reducing agents.