| Literature DB >> 15965468 |
Monica Dentice1, Amitabha Bandyopadhyay, Balázs Gereben, Isabelle Callebaut, Marcelo A Christoffolete, Brian W Kim, Sahar Nissim, Jean-Paul Mornon, Ann Marie Zavacki, Anikó Zeöld, Luciane P Capelo, Cyntia Curcio-Morelli, Rogério Ribeiro, John W Harney, Clifford J Tabin, Antonio C Bianco.
Abstract
WSB-1 is a SOCS-box-containing WD-40 protein of unknown function that is induced by Hedgehog signalling in embryonic structures during chicken development. Here we show that WSB-1 is part of an E3 ubiquitin ligase for the thyroid-hormone-activating type 2 iodothyronine deiodinase (D2). The WD-40 propeller of WSB-1 recognizes an 18-amino-acid loop in D2 that confers metabolic instability, whereas the SOCS-box domain mediates its interaction with a ubiquitinating catalytic core complex, modelled as Elongin BC-Cul5-Rbx1 (ECS(WSB-1)). In the developing tibial growth plate, Hedgehog-stimulated D2 ubiquitination via ECS(WSB-1) induces parathyroid hormone-related peptide (PTHrP), thereby regulating chondrocyte differentiation. Thus, ECS(WSB-1) mediates a mechanism by which 'systemic' thyroid hormone can effect local control of the Hedgehog-PTHrP negative feedback loop and thus skeletogenesis.Entities:
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Year: 2005 PMID： 15965468 PMCID： PMC1761694 DOI： 10.1038/ncb1272
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824