Journal article Open Access

Fanconi anemia protein complex is a novel target of the IKK signalsome

Otsuki, Tetsuya; Young, David B.; Sasaki, Dennis T.; Pando, Matthew P.; Li, Jianwu; Manning, Anthony; Hoekstra, Merl; Hoatlin, Maureen E.; Mercurio, Frank; Liu, Johnson M.

Fanconi anemia (FA), a genetic disorder predisposing to aplastic anemia and cancer, is characterized by hypersensitivity to DNA‐damaging agents and oxidative stress. Five of the cloned FA proteins (FANCA, FANCC, FANCE, FANCF, FANCG) appear to be involved in a common functional pathway that is required for the monoubiquitination of a sixth gene product, FANCD2. Here, we report that FANCA associates with the IκB kinase (IKK) signalsome via interaction with IKK2. Components of the FANCA complex undergo rapid, stimulus‐dependent changes in phosphorylation, which are blocked by kinase‐inactive IKK2 (IKK2 K > M). When exposed to mitomycin C, cells expressing IKK2 K > M develop a cell cycle abnormality characteristic of FA. Thus, FANCA may function to recruit IKK2, thus providing the cell a means of rapidly responding to stress. J. Cell. Biochem. 86: 613–623, 2002
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