Desumoylation Regulates Wnt Signaling

Science's STKE  14 May 2002:
Vol. 2002, Issue 132, pp. tw177
DOI: 10.1126/stke.2002.132.tw177

SUMO is a small protein that can be reversibly attached to proteins, regulating their function, localization, or stability. Kadoya et al. report that the Axin-associated protein, Axam, is a desumoylating enzyme and that this catalytic activity is essential for the ability of Axam to inhibit signaling through the Wnt pathway. Axin is a scaffold that brings β-catenin in close proximity to glycogen synthase kinase 3 (GSK-3), allowing β-catenin to be phosphorylated and targeted for degradation. Axam removed SUMO-1 from proteins in vitro, and in cells, overexpression of Axam caused increases in the pool of free SUMO. Under conditions in which β-catenin was artificially stabilized or in which β-catenin was stabilized in response to a Wnt signal, overexpression of Axam, but not a catalytically inactive mutant, promoted the degradation of β-catenin. In Xenopus embryos, the catalytically inactive mutant of Axam or a truncated Axam were less able to inhibit axis duplication than was wild-type Axam. Inhibition of the expression of the β-catenin target gene samois was also less in the embryos expressing mutated Axam than it was in embryos expressing wild-type Axam. These results suggest that reversible sumoylation is another regulator of the Wnt pathway. For details about Wnt signaling, see the canonical Wnt Pathway and the Xenopus Wnt Pathway in the Connections Maps.

T. Kadoya, H. Yamamoto, T. Suzuki, A. Yukita, A. Fukui, T. Michiue, T. Asahara, K. Tanaka, M. Asashima, A. Kikuchi, Desumoylation activity of Amax, a novel Axin-binding protein, is involved in downregulation of β-catenin. Mol. Cell. Biol. 22, 3803-3819 (2002). [Abstract] [Full Text]

R. Moon, Wnt/β-Catenin Pathway, Science's STKE (Connections Map, as seen in May 2002), [Pathway]

R. Moon, Xenopus Egg Wnt/beta-Catenin Pathway, Science's STKE (Connections Map, as seen in May 2002), [Pathway]