Research article summary (published 14 May 2007):

Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth factor-beta signaling.

Full Abstract

Transforming growth factor-beta (TGF-beta) signaling is controlled by a variety of regulators that target either signaling receptors or activated Smad complexes. Among the negative regulators, Smad7 antagonizes TGF-beta signaling mainly through targeting the signaling receptors, whereas SnoN and c-Ski repress signaling at the transcriptional level through inactivation of Smad complexes. We previously found that Arkadia is a positive regulator of TGF-beta signaling that induces ubiquitin-dependent degradation of Smad7 through its C-terminal RING domain. We report here that Arkadia induces degradation of SnoN and c-Ski in addition to Smad7. Arkadia interacts with SnoN and c-Ski in their free forms as well as in the forms bound to Smad proteins, and constitutively down-regulates levels of their expression. Arkadia thus appears to effectively enhance TGF-beta signaling through simultaneous down-regulation of two distinct types of negative regulators, Smad7 and SnoN/c-Ski, and may play an important role in determining the intensity of TGF-beta family signaling in target cells.

Author information

Author/s: Nagano, Yoshiko (Y); Mavrakis, Konstantinos J (KJ); Lee, Kian Leong (KL); Fujii, Tomoko (T); Koinuma, Daizo (D); Sase, Hitoshi (H); Yuki, Keiko (K); Isogaya, Kazunobu (K); Saitoh, Masao (M); Imamura, Takeshi (T); Episkopou, Vasso (V); Miyazono, Kohei (K); Miyazawa, Keiji (K);

Affiliation: Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of biological chemistry (J Biol Chem), published in United States. (Language: eng)

Reference: 2007-Jul; vol 282 (issue 28) : pp 20492-501

Dates: Created 2007/07/09; Completed 2007/09/13;

PMID: 17510063, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals COS Cells Cercopithecus aethiops DNA-Binding Proteins - genetics; metabolism Down-Regulation - drug effects; physiology Hela Cells Humans Intracellular Signaling Peptides and Proteins - genetics; metabolism

Mice Protein Binding - drug effects; physiology Proto-Oncogene Proteins - genetics; metabolism Signal Transduction - drug effects; physiology Smad7 Protein - genetics; metabolism Transcription, Genetic - drug effects; physiology Transforming Growth Factor beta - metabolism; pharmacology Ubiquitin - genetics; metabolism

Associated Chemicals: Arkadia protein, mouse (0) ; DNA-Binding Proteins (0) ; Intracellular Signaling Peptides and Proteins (0) ; Proto-Oncogene Proteins (0) ; SKIL protein, human (0) ; SMAD7 protein, human (0) ; Smad7 Protein (0) ; Smad7 protein, mouse (0) ; Transforming Growth Factor beta (0) ; Ubiquitin (0) ; SKI protein, human (126648-96-2)

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