Fhit for Action

Science's STKE  30 Mar 2004:
Vol. 2004, Issue 226, pp. tw121-TW121
DOI: 10.1126/stke.2262004TW121

The human FHIT gene is frequently altered in many cancers, and as such, its proposed product, a diadenosine polyphosphate hydrolase, is thought to be a tumor suppressor. Its overexpression suppresses cell growth, and transgenic mice that lack the FHIT gene have a higher incidence of spontaneous tumors. However, the pathway by which Fhit induces apoptosis is still not known, although its tumor suppression effect is independent of its enzymatic activity. Pekarsky et al. examined the amino acid sequence of Fhit and identified a potential phosphorylation site for the cytoplasmic tyrosine kinase Src. Their study demonstrates that Src directly phosphorylates a single tyrosine residue in Fhit in vitro. Overexpression of a constitutively activated form of Src in cultured human embryonic kidney cells resulted in tyrosine phosphorylation of Fhit. Phosphorylated Fhit was also detected in lysates of several normal human tissues and cells, but not in any human tumor cell lines examined. Downstream targets of phosphorylated Fhit that operate in cell growth regulation remain to be determined.

Y. Pekarsky, P. N. Garrison, A. Palamarchuk, N. Zanesi, R. I. Aqeilan, K. Huebner, L. D. Barnes, C. M. Croce, Fhit is a physiological target of the protein kinase Src. Proc. Natl. Acad. Sci. U.S.A. 101, 3775-3779 (2004). [Abstract] [Full Text]