論文 - 詳細
| RRC ID | 2816 |
|---|---|
| 著者 | Menon S, Lee J, Abplanalp WA, Yoo SE, Agui T, Furudate S, Kim PS, Arvan P. |
| タイトル | Oxidoreductase interactions include a role for ERp72 engagement with mutant thyroglobulin from the rdw/rdw rat dwarf. |
| ジャーナル | J Biol Chem |
| Abstract |
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. |
| 巻・号 | 282(9) |
| ページ | 6183-91 |
| 公開日 | 2007-3-2 |
| DOI | 10.1074/jbc.M608863200 |
| PII | S0021-9258(20)52226-6 |
| PMID | 17200118 |
| PMC | PMC2542443 |
| MeSH | Animals Apoptosis Dwarfism / etiology* Dwarfism / metabolism Endoplasmic Reticulum Goiter Membrane Glycoproteins / genetics Membrane Glycoproteins / metabolism* Mutation, Missense Oxidoreductases / metabolism* Protein Binding Protein Transport Rats Rats, Mutant Strains Thyroglobulin / genetics* Thyroglobulin / metabolism Thyroid Gland / cytology |
| IF | 4.238 |
| 引用数 | 35 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ラット | F344.WIC-Tgrdw/Kts(strainID=1037) |