Editors' ChoiceApoptosis

FANCC-Free STAT1 Is Less Active

See allHide authors and affiliations

Science's STKE  20 Jun 2000:
Vol. 2000, Issue 37, pp. tw7
DOI: 10.1126/stke.2000.37.tw7

Fanconi anemia group C (FA-C) patients, who lack expression of the FANCC protein, have hematopoietic progenitor cells that are hypersensitive to IFN-γ-mediated apoptosis. In vitro this problem can be corrected by transfection of FANCC into FA-C cells. STAT1 is not activated in IFN-γ-treated FA-C cells. Pang et al. sought to find the role of FANCC in STAT1 activation. STAT1 did not coimmunoprecipitate with the IFN-γ receptor alpha chain (IFNγRα) in IFN-γ-treated FA-C cells; however, reconstitution of FANCC in FA-C cells led to the association of STAT1 and IFNγRα. Glutathione-S-transferase (GST)-FANCC fusion proteins were able to associate with STAT1 from IFN-γ-treated FA-C cell lysates, which suggested that the function of FANCC is to aid STAT1 in docking to IFNγRα. Subsequent work by the authors demonstrated that, in unstimulated cells, FANCC was associated with STAT1; activation of IFNγRα led to the recruitment of FANCC and STAT1, whereupon STAT1 became phosphorylated while still complexed to FANCC.

Pang, Q., Fagerlie, S., Christianson, T.A., Keeble, W., Faulkner, G., Diaz, J., Rathbun, R.K., and Bagby, G.C. (2000) The Fanconi anemia protein FANCC binds to and facilitates the activation of STAT1 by gamma Interferon and hematopoietic growth factors. Mol. Cell. Biol. 20: 4724 -4735. [Abstract] [Full Text]

Stay Connected to Science Signaling