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

被引：185

作者：

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

机构：

[1] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Thyroid Sect, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[3] Hungarian Acad Sci, Inst Expt Med, Lab Endocrine Neurobiol, H-1083 Budapest, Hungary

[4] Univ Paris 06, Dept Biol Struct, LMCP, CNRS,UMR7590, F-75252 Paris, France

[5] Univ Paris 07, Dept Biol Struct, LMCP, CNRS,UMR7590, F-75252 Paris, France

来源：

NATURE CELL BIOLOGY | 2005年 / 7卷 / 07期

关键词：

D O I：

10.1038/ncb1272

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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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页码：698 / U87

页数：9

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