MilliporeSigma
  • Home
  • Search Results
  • Arkadia enhances BMP signalling through ubiquitylation and degradation of Smad6.

Arkadia enhances BMP signalling through ubiquitylation and degradation of Smad6.

Journal of biochemistry (2015-03-13)
Yutaro Tsubakihara, Atsuhiko Hikita, Shin Yamamoto, Sachi Matsushita, Natsuki Matsushita, Yusuke Oshima, Keiji Miyazawa, Takeshi Imamura
ABSTRACT

Arkadia, a positive regulator of Smad-dependent signalling via the transforming growth factor-β (TGF-β) family, is an E3 ubiquitin ligase that induces ubiquitylation and proteasome-dependent degradation of TGF-β suppressors such as Smad7, c-Ski and SnoN. In this study, we examined the effects of Arkadia on bone morphogenetic protein (BMP)-induced osteoblast differentiation. Knockdown of Arkadia reduced mineralization and expression of osteoblast differentiation markers. Furthermore, we showed that Smad6, a BMP-specific inhibitory Smad, is a target of Arkadia: wild-type (WT) Arkadia, but not the C937A (CA) mutant lacking E3 ubiquitin-ligase activity, induced ubiquitylation and proteasome-dependent degradation of Smad6. Accordingly, protein levels of Smad6, Smad7 and c-Ski were elevated in MEFs from Arkadia KO mice. Finally, expression of Arkadia attenuated blockade of BMP signalling by Smad6 in a transcriptional reporter assay. These results demonstrate that Smad6 is a novel target of Arkadia, and that Arkadia positively regulates BMP signalling via degradation of Smad6, Smad7 and c-Ski/SnoN.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
SAFC
L-Glutamine
Sigma-Aldrich
L-Glutamine
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, anhydrous, ≥99% (titration)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, 99.995% trace metals basis
Sigma-Aldrich
N,N-Dimethylformamide, ACS reagent, ≥99.8%
Sigma-Aldrich
N,N-Dimethylformamide, anhydrous, 99.8%
Sigma-Aldrich
1-Naphthol, ReagentPlus®, ≥99%
Sigma-Aldrich
1-Naphthol, BioXtra, ≥99%
Sigma-Aldrich
N,N-Dimethylformamide, for molecular biology, ≥99%
Sigma-Aldrich
1-Naphthol, puriss. p.a., reag. Ph. Eur., ≥99% (GC)
Sigma-Aldrich
N,N-Dimethylformamide, suitable for HPLC, ≥99.9%