Literature DB >> 10587642

Ubiquitin-dependent degradation of TGF-beta-activated smad2.

R S Lo1, J Massagué.   

Abstract

SMAD proteins are phosphorylated by transforming growth factor-beta (TGF-beta) receptors and translocate to the nucleus, where they control transcription. Here we investigate the fate of activated Smad2. We show that receptor-mediated activation leads to multi-ubiquitination and subsequent degradation of Smad2 by the proteasome. Ubiquitination of Smad2 is a consequence of its accumulation in the nucleus. If degradation is averted, the phosphorylated Smad2 remains in the nucleus in an active state. By targeting Smad2 for destruction, TGF-beta ensures the irreversible termination of its own signalling function.

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Year:  1999        PMID： 10587642     DOI： 10.1038/70258

Source DB:  PubMed          Journal:  Nat Cell Biol        ISSN： 1465-7392            Impact factor:   28.824


  108 in total

1.  Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase.

Authors:  Y Zhang; C Chang; D J Gehling; A Hemmati-Brivanlou; R Derynck
Journal:  Proc Natl Acad Sci U S A       Date:  2001-01-30       Impact factor: 11.205

Review 2.  Transcriptional control by the TGF-beta/Smad signaling system.

Authors:  J Massagué; D Wotton
Journal:  EMBO J       Date:  2000-04-17       Impact factor: 11.598

3.  Smad proteins and hepatocyte growth factor control parallel regulatory pathways that converge on beta1-integrin to promote normal liver development.

Authors:  M Weinstein; S P Monga; Y Liu; S G Brodie; Y Tang; C Li; L Mishra; C X Deng
Journal:  Mol Cell Biol       Date:  2001-08       Impact factor: 4.272

Review 4.  TGF-beta-mediated control of allergen-specific T-cell responses.

Authors:  Carsten B Schmidt-Weber; Steffen Kunzmann; Kurt Blaser
Journal:  Curr Allergy Asthma Rep       Date:  2002-05       Impact factor: 4.806

5.  Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN.

Authors:  S L Stroschein; S Bonni; J L Wrana; K Luo
Journal:  Genes Dev       Date:  2001-11-01       Impact factor: 11.361

6.  Ligand-dependent degradation of Smad3 by a ubiquitin ligase complex of ROC1 and associated proteins.

Authors:  M Fukuchi; T Imamura; T Chiba; T Ebisawa; M Kawabata; K Tanaka; K Miyazono
Journal:  Mol Biol Cell       Date:  2001-05       Impact factor: 4.138

7.  Transformation by E1A oncoprotein involves ubiquitin-mediated proteolysis of the neuronal and tumor repressor REST in the nucleus.

Authors:  Hancheng Guan; Robert P Ricciardi
Journal:  J Virol       Date:  2012-03-14       Impact factor: 5.103

8.  Dynamics of TGF-β signaling reveal adaptive and pulsatile behaviors reflected in the nuclear localization of transcription factor Smad4.

Authors:  Aryeh Warmflash; Qixiang Zhang; Benoit Sorre; Alin Vonica; Eric D Siggia; Ali H Brivanlou
Journal:  Proc Natl Acad Sci U S A       Date:  2012-06-11       Impact factor: 11.205

9.  Combination therapy with VELCADE and tissue plasminogen activator is neuroprotective in aged rats after stroke and targets microRNA-146a and the toll-like receptor signaling pathway.

Authors:  Li Zhang; Michael Chopp; Xianshuang Liu; Hua Teng; Tao Tang; Haifa Kassis; Zheng Gang Zhang
Journal:  Arterioscler Thromb Vasc Biol       Date:  2012-06-21       Impact factor: 8.311

10.  Morphogen gradient interpretation by a regulated trafficking step during ligand-receptor transduction.

Authors:  Jerome Jullien; John Gurdon
Journal:  Genes Dev       Date:  2005-10-31       Impact factor: 11.361
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