Editors' ChoiceImmunology

A Shocking Interaction in Fanconi Anemia

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Science's STKE  21 Aug 2001:
Vol. 2001, Issue 96, pp. tw6
DOI: 10.1126/stke.2001.96.tw6

Mutations in the FANCC gene are linked to the bone marrow failure that patients suffering from Fanconi anemia (FA) exhibit. The FANCC protein is thought to increase the survival response of hematopoietic cells to cytokines and growth factors and also to protect cells from the cytotoxic effects of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), but its mechanisms of action are not known. Pang et al. show that the FANCC protein binds to the molecular chaperone heat shock protein 70 (Hsp70), which also protects cells from environmental stress. The interaction in lymphoblasts required the chaperone cofactor Hsp40. Treatment of cells with IFN-γ or TNF-α increased complex formation, and repression of Hsp70 expression caused cells to become hypersensitive to the apoptoic effects of these cytokines. The downstream signaling events remain unclear, but the authors speculate that the FANCC-Hsp70-Hsp40 interaction may be required to initiate Hsp70-dependent antiapoptotic signaling.

Q. Pang, W. Keeble, T.A. Christianson, G.R. Faulkner, G.C. Bagby, FANCC interacts with Hsp70 to protect hematopoietic cells from INF-γ/TNF-α-mediated cytotoxicity. EMBO J. 20: 4478-4489 (2001). [Abstract] [Full Text]

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