Arkadia--beyond the TGF-β pathway.
Arkadia, also known as ring finger 111 (Rnf111), is an E3 ubiquitin ligase that amplifies transforming growth factor (TGF)-β family signalling through degradation of negative TGF-β signal regulators, i.e. Smad7, c-Ski and SnoN. Arkadia plays critical roles in early embryonic development through modulation of nodal signalling, as well as progression of tissue fibrosis and cancer through regulation of TGF-β signalling. Recent findings suggest that, similar to other ubiquitin ligases, including Smurf1 and 2, Arkadia regulates signalling pathways other than those of the TGF-β family. Arkadia interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signalling pathways.
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. miyazono@m.u-tokyo.ac.jp
Kohei
K
Miyazono
Daizo
D
Koinuma
D000818:Animals; D004705:Endocytosis / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology*; D015398:Signal Transduction; D055411:TGF-beta Superfamily Proteins / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D054875:Ubiquitination
D009687:Nuclear Proteins; D055411:TGF-beta Superfamily Proteins; C486067:RNF111 protein, human; D044767:Ubiquitin-Protein Ligases; D066246:ErbB Receptors