Oxidoreductase interactions include a role for ERp72 engagement with mutant thyroglobulin from the rdw/rdw rat dwarf.

Oxidoreductase interactions include a role for ERp72 engagement with mutant thyroglobulin from the rdw/rdw rat dwarf. Research Abstract Details 

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Oxidoreductase interactions include a role for ERp72 engagement with mutant thyroglobulin from the rdw/rdw rat dwarf. Abstract Text:

Shekar Menon,Jaemin Lee,William A Abplanalp,Sung-Eun Yoo,Takashi Agui,Sen-Ichi Furudate,Paul S Kim,Peter Arvan,

Newly synthesized thyroglobulin (Tg), the secretory glycoprotein that serves as precursor in thyroid hormone synthesis, normally forms transient covalent protein complexes with oxidoreductases of the endoplasmic reticulum (ER). The Tg-G2320R mutation is responsible for congenital hypothyroidism in rdw/rdw rats, in which a lack of secondary thyroid enlargement (goiter) implicates death of thyrocytes as part of disease pathogenesis. We found that mutant Tg-G2320R was retained within the ER with no detectable synthesis of thyroxine, had persistent exposure of free cysteine thiols, and was associated with activated ER stress response but incomplete ER-associated degradation (ERAD). Tg-G2320R associated with multiple ER resident proteins, most notably ERp72, including covalent Tg-ERp72 interactions. In PC Cl3 thyrocytes, inducible overexpression of ERp72 increased the ability of cells to maintain Tg cysteines in a reduced state. Noncovalent interactions of several ER chaperones with newly synthesized Tg-G2320R diminished over time in parallel with ERAD of the mutant protein, yet a small ERAD-resistant Tg fraction remained engaged in covalent association with ERp72 even 2 days post-synthesis. Such covalent protein aggregates may set the stage for apoptotic thyrocyte cell death, preventing thyroid goiter formation in rdw/rdw rats.

Oxidoreductase interactions include a role for ERp72 engagement with mutant thyroglobulin from the rdw/rdw rat dwarf. Publishing Authors By Initials

S Menon,J Lee,WA Abplanalp,SE Yoo,T Agui,S Furudate,PS Kim,P Arvan,

For similar endocrine system: endocrine glands: thyroid gland research abstracts see: endocrine system: endocrine glands: thyroid gland research

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Oxidoreductase interactions include a role for ERp72 engagement with mutant thyroglobulin from the rdw/rdw rat dwarf. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 6183-91

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 2

MONTH: 01

YEAR: 2007

Oxidoreductase interactions include a role for ERp72 engagement with mutant thyroglobulin from the rdw/rdw rat dwarf. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

Oxidoreductase interactions include a role for ERp72 engagement with mutant thyroglobulin from the rdw/rdw rat dwarf. Keywords Mesh Terms:

KEYWORDS: Thyroid Gland

MESH TERMS: cytology

Chemical & Substance for Abstract: Oxidoreductase interactions include a role for ERp72 engagement with mutant thyroglobulin from the rdw/rdw rat dwarf. Information

Substance Name: Oxidoreductases

Registry Number: EC 1.-

Grant and Affiliation Information for Oxidoreductase interactions include a role for ERp72 engagement with mutant thyroglobulin from the rdw/rdw rat dwarf.

AFFILIATION: Program in Cell and Molecular Biology and Division of Endocrinology, University of Cincinnati, Ohio 45267, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: DK52076

ACRONYM: DK

MEDLINETA: J Biol Chem

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