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Sci. STKE, 7 December 1999
Vol. 1999, Issue 11, p. tw4
[DOI: 10.1126/stke.1999.11.tw4]


Cell Biology Terminating SMAD Signals

SMADs function with other proteins to mediate transcriptional activation in response to transforming growth factor β and related proteins. SMADs are activated when phosphorylated by the TGF-β receptor, so one might have thought that the easy way to inactivate SMADs would be to dephosphorylate them. Although dephosphorylation might be a factor, new evidence points instead to a major role for ubiquitin-dependent degradation in termination of SMAD signaling. Lo and Massagué find that degradation of SMAD2 is increased in response to activation of the TGF-β receptor. Unlike regulation of some other transcription factors for which phosphorylation is a key tag that leads to ubiquitination and destruction, the essential event that leads to degradation of SMAD2 appears to be its translocation to the nucleus. The regulation of SMAD2 is also distinct from that recently described by Zhu et al. for SMAD1 and SMAD5, which appears to rely not on nuclear localization, but rather a cytoplasmic event that depends on a Pro-Tyr (PY) motif in the SMAD proteins. All the findings are summarized in an insightful "News and Views" by Heldin and ten Dijke.

Lo, R.S., and Massagué, J. (1999) Ubiquitin-dependent degradation of TGF-β-activated Smad2. Nature Cell Biol. 1: 472-478. [Online Journal]

Zhu, H., Kavsak, P., Abdollah, S., Wrana, J.L., and Thomsen, G.H. (1999) A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature 400: 687-693. [Online Journal]

Heldin, C.-H., and ten Dijke, P. (1999) SMAD destruction turns off signalling. Nature Cell Biol. 1: E195 - E197. [Online Journal]

Citation: Terminating SMAD Signals. Sci. STKE 1999, tw4 (1999).

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