Mutations in the deubiquitinase gene USP8 cause Cushing's disease
書誌事項
- 公開日
- 2014-12-08
- 資源種別
- journal article
- 権利情報
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- http://www.springer.com/tdm
- DOI
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- 10.1038/ng.3166
- 公開者
- Springer Science and Business Media LLC
この論文をさがす
説明
Cushing's disease is caused by corticotroph adenomas of the pituitary. To explore the molecular mechanisms of endocrine autonomy in these tumors, we performed exome sequencing of 10 corticotroph adenomas. We found somatic mutations in the USP8 deubiquitinase gene in 4 of 10 adenomas. The mutations clustered in the 14-3-3 protein binding motif and enhanced the proteolytic cleavage and catalytic activity of USP8. Cleavage of USP8 led to increased deubiqutination of the EGF receptor, impairing its downregulation and sustaining EGF signaling. USP8 mutants enhanced promoter activity of the gene encoding proopiomelanocortin. In summary, our data show that dominant mutations in USP8 cause Cushing's disease via activation of EGF receptor signaling.
収録刊行物
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- Nature Genetics
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Nature Genetics 47 (1), 31-38, 2014-12-08
Springer Science and Business Media LLC
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キーワード
- Adenoma
- Pro-Opiomelanocortin
- Molecular Sequence Data
- Adrenocorticotropic Hormone
- Chlorocebus aethiops
- Endopeptidases
- Animals
- Humans
- Exome
- Pituitary Neoplasms
- Amino Acid Sequence
- Pituitary ACTH Hypersecretion
- Endosomal Sorting Complexes Required for Transport
- Sequence Homology, Amino Acid
- Neoplasm Proteins
- ErbB Receptors
- Gene Expression Regulation, Neoplastic
- ACTH-Secreting Pituitary Adenoma
- 14-3-3 Proteins
- COS Cells
- Mutation
- Sequence Alignment
- Ubiquitin Thiolesterase
詳細情報 詳細情報について
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- CRID
- 1360565166759872384
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- DOI
- 10.1038/ng.3166
-
- ISSN
- 15461718
- 10614036
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- PubMed
- 25534197
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- 資料種別
- journal article
-
- データソース種別
-
- Crossref
- KAKEN
- OpenAIRE
