論文 - 詳細
| RRC ID | 46625 |
|---|---|
| 著者 | Koon JC, Kubiseski TJ. |
| タイトル | Developmental arrest of Caenorhabditis elegans BRAP-2 mutant exposed to oxidative stress is dependent on BRC-1. |
| ジャーナル | J Biol Chem |
| Abstract |
Oxidative damage by reactive oxygen species is believed to be a contributor to the development of cancer and the physiological deterioration associated with aging. In this report, we describe the effect of reactive oxygen species exposure to a developing Caenorhabditis elegans organism containing a deletion in the homolog of BRCA1-associated protein 2 (BRAP-2). A mutant containing a deletion of brap-2 was highly sensitive to oxidizing conditions and demonstrated early larval arrest and lethality at low concentrations of the oxidative stress-inducing drug paraquat compared with the wild-type. This developmental arrest occurred early in the L1 stage and was dependent specifically on the function of the C. elegans ortholog of BRCA-1 tumor suppressor brc-1. We also show that developmental arrest in brap-2 mutants when exposed to oxidative stress was due to enhanced expression levels of the cell cycle inhibitor cki-1, and this increase in the expression levels of cki-1 requires brc-1 in brap-2 mutant animals. Our findings demonstrate that BRAP-2 is necessary for preventing an inappropriate response to elevated levels of reactive oxygen species by countering premature activation of BRC-1 and CKI-1. |
| 巻・号 | 285(18) |
| ページ | 13437-43 |
| 公開日 | 2010-4-30 |
| DOI | 10.1074/jbc.M110.107011 |
| PII | S0021-9258(19)62594-9 |
| PMID | 20207739 |
| PMC | PMC2859503 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / genetics Carrier Proteins / metabolism* Cyclin-Dependent Kinase Inhibitor Proteins / genetics Cyclin-Dependent Kinase Inhibitor Proteins / metabolism Gene Expression Regulation, Developmental / drug effects Gene Expression Regulation, Developmental / physiology* Herbicides / pharmacology Larva / genetics Larva / metabolism Mutation* Oxidative Stress / drug effects Oxidative Stress / physiology* Paraquat / pharmacology Reactive Oxygen Species / metabolism* |
| IF | 4.238 |
| 引用数 | 9 |
| 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 |
| リソース情報 | |
| 線虫 | tm1145 |