2. Academic Validation
  3. The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate

The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate

  • Nat Cell Biol. 2005 Jul;7(7):698-705. doi: 10.1038/ncb1272.
Monica Dentice 1,  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
Affiliations

Affiliation

  • 1 Thyroid Section, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
PMID: 15965468 DOI: 10.1038/ncb1272
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.

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