Mol Biol Cell 2001,
PMID: 11359933
Fukuchi, M; Imamura, T; Chiba, T; Ebisawa, T; Kawabata, M; Tanaka, K; Miyazono, K
Smads are signal mediators for the members of the transforming growth factor-beta (TGF-beta) superfamily. Upon phosphorylation by the TGF-beta receptors, Smad3 translocates into the nucleus, recruits transcriptional coactivators and corepressors, and regulates transcription of target genes. Here, we show that Smad3 activated by TGF-beta is degraded by the ubiquitin-proteasome pathway. Smad3 interacts with a RING finger protein, ROC1, through its C-terminal MH2 domain in a ligand-dependent manner. An E3 ubiquitin ligase complex ROC1-SCF(Fbw1a) consisting of ROC1, Skp1, Cullin1, and Fbw1a (also termed betaTrCP1) induces ubiquitination of Smad3. Recruitment of a transcriptional coactivator, p300, to nuclear Smad3 facilitates the interaction with the E3 ligase complex and triggers the degradation process of Smad3. Smad3 bound to ROC1-SCF(Fbw1a) is then exported from the nucleus to the cytoplasm for proteasomal degradation. TGF-beta/Smad3 signaling is thus irreversibly terminated by the ubiquitin-proteasome pathway.
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Text Mining Data
Dashed line = No text mining data
Manually curated Databases
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IRef Biogrid Interaction:
RBX1
—
SMAD3
(direct interaction, two hybrid)
-
IRef Biogrid Interaction:
RBX1
—
SMAD3
(physical association, affinity chromatography technology)
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IRef Biogrid Interaction:
UBC
—
SMAD3
(physical association, affinity chromatography technology)
-
MIPS CORUM Ubiquitin E3 ligase (SMAD3, BTRC, CUL1, SKP1A, RBX1):
Ubiquitin E3 ligase (SMAD3, BTRC, CUL1, SKP1A, RBX1) complex (BTRC-CUL1-RBX1-SKP1-SMAD3)
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IRef Corum Interaction:
Complex of RBX1-SKP1-SMAD3-CUL1-BTRC
(association, coimmunoprecipitation)
-
IRef Hprd Interaction:
Complex of 26 proteins
(in vivo)
-
IRef Hprd Interaction:
CUL1
—
SMAD3
(in vivo)
-
IRef Hprd Interaction:
RBX1
—
SMAD3
(in vitro)
-
IRef Hprd Interaction:
RBX1
—
SMAD3
(in vivo)
-
IRef Hprd Interaction:
RBX1
—
SMAD3
(two hybrid)
-
IRef Hprd Interaction:
BTRC
—
SMAD3
(in vivo)
In total, 11 gene pairs are associated to this article in curated databases