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

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

• Book ID: 102300126
• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 282 KB
• Volume: 86
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.10270

✦ Synopsis

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 IkappaB 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.