Revisao
Fanconi anemia (FA) is an autosomal recessive disorder characterized by bone marrow failure, birth defects and chromsomal instability. The FA Group C complementation group gene encodes the protein FANCC, which is located in both cytoplasmic and nuclear compartments. FANCC is expressed in a cell cycle-dependent manner, with the lowest levels at the G1/S boundary and the highest levels in the M-phase. The FANCC protein interacts with other FA complementation group proteins as well as non-FA proteins. A 230 kDa human alpha spectrin II acts as a scaffold to enhance interactions between FANCC and FANCA to form a nuclear complex. Another binding partner of FANCC is the BTB/POZ domain containing protein FAZF, which is a transcriptional repressor. In hematopoietic cells expressing mutant FANCC, PKR is constitutively phosphorylated and has increased binding affinity for double-stranded RNA, which suggests that FANCC indirectly suppresses the activity of PKR. These cells are apoptotic and are hypersensitive to IFNgamma and TNFalpha. In addition, FANCC protein is involved in the activation of STAT1 through receptors for at least three hematopoietic growth and survival factors.