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

Monica Dentice; 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

doi:10.1038/ncb1272

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

Monica Dentice
, 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

Research output: Contribution to journal › Article › peer-review

201 Scopus citations

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.

Original language	English (US)
Pages (from-to)	698-705
Number of pages	8
Journal	Nature Cell Biology
Volume	7
Issue number	7
DOIs	https://doi.org/10.1038/ncb1272
State	Published - Jul 2005
Externally published	Yes

ASJC Scopus subject areas

Cell Biology

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Dentice, M., Bandyopadhyay, A., Gereben, B., Callebaut, I., Christoffolete, M. A., Kim, B. W., Nissim, S., Mornon, J. P., Zavacki, A. M., Zeöld, A., Capelo, L. P., Curcio-Morelli, C., Ribeiro, R., Harney, J. W., Tabin, C. J., & Bianco, A. C. (2005). The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate. Nature Cell Biology, 7(7), 698-705. https://doi.org/10.1038/ncb1272

Dentice, M, Bandyopadhyay, A, Gereben, B, Callebaut, I, Christoffolete, MA, Kim, BW, Nissim, S, Mornon, JP, Zavacki, AM, Zeöld, A, Capelo, LP, Curcio-Morelli, C, Ribeiro, R, Harney, JW, Tabin, CJ & Bianco, AC 2005, 'The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate', Nature Cell Biology, vol. 7, no. 7, pp. 698-705. https://doi.org/10.1038/ncb1272

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

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 (ECSWSB-1). In the developing tibial growth plate, Hedgehog-stimulated D2 ubiquitination via ECSWSB-1 induces parathyroid hormone-related peptide (PTHrP), thereby regulating chondrocyte differentiation. Thus, ECSWSB-1 mediates a mechanism by which 'systemic' thyroid hormone can effect local control of the Hedgehog-PTHrP negative feedback loop and thus skeletogenesis.",

author = "Monica Dentice and Amitabha Bandyopadhyay and Bal{\'a}zs Gereben and Isabelle Callebaut and Christoffolete, \{Marcelo A.\} and Kim, \{Brian W.\} and Sahar Nissim and Mornon, \{Jean Paul\} and Zavacki, \{Ann Marie\} and Anik{\'o} Ze{\"o}ld and Capelo, \{Luciane P.\} and Cyntia Curcio-Morelli and Rog{\'e}rio Ribeiro and Harney, \{John W.\} and Tabin, \{Clifford J.\} and Bianco, \{Antonio C.\}",

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AU - Bandyopadhyay, Amitabha

AU - Gereben, Balázs

AU - Callebaut, Isabelle

AU - Christoffolete, Marcelo A.

AU - Kim, Brian W.

AU - Nissim, Sahar

AU - Mornon, Jean Paul

AU - Zavacki, Ann Marie

AU - Zeöld, Anikó

AU - Capelo, Luciane P.

AU - Curcio-Morelli, Cyntia

AU - Ribeiro, Rogério

AU - Harney, John W.

AU - Tabin, Clifford J.

AU - Bianco, Antonio C.

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N2 - 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 (ECSWSB-1). In the developing tibial growth plate, Hedgehog-stimulated D2 ubiquitination via ECSWSB-1 induces parathyroid hormone-related peptide (PTHrP), thereby regulating chondrocyte differentiation. Thus, ECSWSB-1 mediates a mechanism by which 'systemic' thyroid hormone can effect local control of the Hedgehog-PTHrP negative feedback loop and thus skeletogenesis.

AB - 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 (ECSWSB-1). In the developing tibial growth plate, Hedgehog-stimulated D2 ubiquitination via ECSWSB-1 induces parathyroid hormone-related peptide (PTHrP), thereby regulating chondrocyte differentiation. Thus, ECSWSB-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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The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate

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