論文 - 詳細
| RRC ID | 41367 |
|---|---|
| 著者 | Motyckova G, Weilbaecher KN, Horstmann M, Rieman DJ, Fisher DZ, Fisher DE. |
| タイトル | Linking osteopetrosis and pycnodysostosis: regulation of cathepsin K expression by the microphthalmia transcription factor family. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
Various genetic conditions produce dysfunctional osteoclasts resulting in osteopetrosis or osteosclerosis. These include human pycnodysostosis, an autosomal recessive syndrome caused by cathepsin K mutation, cathepsin K-deficient mice, and mitf mutant rodent strains. Cathepsin K is a highly expressed cysteine protease in osteoclasts that plays an essential role in the degradation of protein components of bone matrix. Cathepsin K also is expressed in a significant fraction of human breast cancers where it could contribute to tumor invasiveness. Mitf is a member of a helix-loop-helix transcription factor subfamily, which contains the potential dimerization partners TFE3, TFEB, and TFEC. In mice, dominant negative, but not recessive, mutations of mitf, produce osteopetrosis, suggesting a functional requirement for other family members. Mitf also has been found-and TFE3 has been suggested-to modulate age-dependent changes in osteoclast function. This study identifies cathepsin K as a transcriptional target of Mitf and TFE3 via three consensus elements in the cathepsin K promoter. Additionally, cathepsin K mRNA and protein were found to be deficient in mitf mutant osteoclasts, and overexpression of wild-type Mitf dramatically up-regulated expression of endogenous cathepsin K in cultured human osteoclasts. Cathepsin K promoter activity was disrupted by dominant negative, but not recessive, mouse alleles of mitf in a pattern that closely matches their osteopetrotic phenotypes. This relationship between cathepsin K and the Mitf family helps explain the phenotypic overlap of their corresponding deficiencies in pycnodysostosis and osteopetrosis and identifies likely regulators of cathepsin K expression in bone homeostasis and human malignancy. |
| 巻・号 | 98(10) |
| ページ | 5798-803 |
| 公開日 | 2001-5-8 |
| DOI | 10.1073/pnas.091479298 |
| PII | 091479298 |
| PMID | 11331755 |
| PMC | PMC33293 |
| MeSH | Alleles Animals Base Sequence Cathepsin K Cathepsins / genetics* Cathepsins / metabolism DNA DNA-Binding Proteins / genetics DNA-Binding Proteins / physiology* Gene Expression Regulation, Enzymologic / physiology* Mice Mice, Inbred C57BL Microphthalmia-Associated Transcription Factor Molecular Sequence Data Osteopetrosis / enzymology Osteopetrosis / genetics* Promoter Regions, Genetic RNA, Messenger / genetics Transcription Factors* Transcription, Genetic / physiology |
| IF | 9.412 |
| 引用数 | 167 |
| WOS 分野 | CELL 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 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 | |
| ヒト・動物細胞 | ST2(RCB0224) |