Transcriptional induction of Smurf2 ubiquitin ligase by TGF-beta.

Abstract:

:Smad ubiquitination regulatory factor 2 (Smurf2), a ubiquitin ligase for Smads, plays critical roles in the regulation of transforming growth factor-beta (TGF-beta)-Smad signaling via ubiquitin-dependent degradation of Smad2 and Smad7. We found that TGF-beta stimulates Smurf2 expression. TGF-beta activated the Smurf2 promoter in a TGF-beta responsive cell lines, whereas IL-1alpha, PDGF and epidermal growth factor did not. TGF-beta-mediated Smurf2 promoter activation was inhibited by Smad7 or an activin receptor-like kinase 5 inhibitor but not by dominant negative Smad or disruption of Smad-binding elements in the promoter. Moreover, inhibition of the phosphatidil inositol 3 kinase (PI3K)/Akt pathway suppressed TGF-beta-mediated Smurf2 induction. These results suggest that TGF-beta stimulates Smurf2 expression by Smad-independent pathway such as PI3K/Akt pathway via TGF-beta receptor.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Ohashi N,Yamamoto T,Uchida C,Togawa A,Fukasawa H,Fujigaki Y,Suzuki S,Kitagawa K,Hattori T,Oda T,Hayashi H,Hishida A,Kitagawa M

doi

10.1016/j.febslet.2005.03.069

keywords:

subject

Has Abstract

pub_date

2005-05-09 00:00:00

pages

2557-63

issue

12

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(05)00421-7

journal_volume

579

pub_type

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