Roles of mono-ubiquitinated Smad4 in the formation of Smad transcriptional complexes

Journal Article · Fri Nov 14 04:00:00 UTC 2008 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2008.08.143· OSTI ID:21217097

Bei, Wang ^[1]; Suzuki, Hiroyuki ^[1]; Kato, Mitsuyasu ^[1]

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1. Department of Experimental Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki 305-8575 (Japan)

TGF-{beta} activates receptor-regulated Smad (R-Smad) through phosphorylation by type I receptors. Activated R-Smad binds to Smad4 and the complex translocates into the nucleus and stimulates the transcription of target genes through association with co-activators including p300. It is not clear, however, how activated Smad complexes are removed from target genes. In this study, we show that TGF-{beta} enhances the mono-ubiquitination of Smad4. Smad4 mono-ubiquitination was promoted by p300 and suppressed by the c-Ski co-repressor. Smad4 mono-ubiquitination disrupted the interaction with Smad2 in the presence of constitutively active TGF-{beta} type I receptor. Furthermore, mono-ubiquitinated Smad4 was not found in DNA-binding Smad complexes. A Smad4-Ubiquitin fusion protein, which mimics mono-ubiquitinated Smad4, enhanced localization to the cytoplasm. These results suggest that mono-ubiquitination of Smad4 occurs in the transcriptional activator complex and facilitates the turnover of Smad complexes at target genes.

• OSTI ID: 21217097
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 376; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
COMPLEXES
CYTOPLASM
DNA
GENES
INTERACTIONS
PHOSPHORYLATION
RECEPTORS
TRANSCRIPTION