New Regulator of Wnt Signaling

Science's STKE  29 Apr 2003:
Vol. 2003, Issue 180, pp. tw170-TW170
DOI: 10.1126/stke.2003.180.tw170

The Wingless or Wnt signaling pathway has crucial functions in development and also contributes to formation of certain human cancers. The β-catenin protein functions in the Wnt pathway as a coactivator of transcription where it works with the transcription factors Tcf and Lef. Takemaru et al. conducted a screen for proteins that interact with β-catenin and isolated a protein they call Chibby. The protein is evolutionarily conserved from flies to humans. In Drosophila, inhibition of Chibby function by RNA interference caused developmental defects like those known to occur when Wnt signaling is overstimulated. Epistasis experiments placed Chibby action downstream of wingless and uptream of β-catenin. In co-transfection experiments in mammalian HEK 293 cells, Chibby competed with Lef-1 for binding to β-catenin, providing a potential mechanism for its inhibitory actions. Thus, Chibby appears to be a new physiological regulator of Wnt signaling. The authors cite preliminary studies indicating that expression of Chibby is reduced in some cancers, supporting a potential role for Chibby as a tumor suppressor.

K.-I. Takemaru, S. Yamaguchi, Y. S. Lee, Y. Zhang, R. W. Carthew, R. T. Moon, Chibby, a nuclear β-catenin-associated antagonist of the Wnt/Wingless pathway. Nature 422, 905-909 (2003). [Online Journal]