ArticleNeuroendocrinology2020
Ubiquitin-Specific Protease 8 Mutant Corticotrope Adenomas Present Unique Secretory and Molecular Features and Shed Light on the Role of Ubiquitylation on ACTH Processing.
Article in Neuroendocrinology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Targeted analysis of Ubiquitin-Specific Peptidase (USP8) in a population of Iranian people with Cushing's disease and a systematic review of the literature.BMC endocrine disorders · 2024Pooled it
- Differential expression of POMC-processing genes in corticotroph tumors.Endocrine oncology (Bristol, England) · 2026Article
- Deciphering USP8's pivotal role in cancer: mechanisms, clinical insights and contrasts with its function in pituitary adenomas.Journal of translational medicine · 2025Review
- Management of Cushing's disease in the initial phase~From detection to surgery~.Endocrine journal · 2025Review
- Clinical Implications of Molecular and Genetic Biomarkers in Cushing's Disease: A Literature Review.Journal of clinical medicine · 2025Review
- Grading and staging for pituitary neuroendocrine tumors.Brain pathology (Zurich, Switzerland) · 2025Review
- Cushing's Disease Manifestation inInternational journal of molecular sciences · 2024Article
- Article
- New Trends in Treating Cushing's Disease.TouchREVIEWS in endocrinology · 2024Article
- Relevance of mutations in protein deubiquitinases genes andFrontiers in endocrinology · 2024Article
- Review
- Review
- Silibinin, an HSP90 Inhibitor, on Human ACTH-Secreting Adenomas.Neuroendocrinology · 2023Article
- Genetic drivers of Cushing's disease: Frequency and associated phenotypes.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- Molecular Derangements and the Diagnosis of ACTH-Dependent Cushing's Syndrome.Endocrine reviews · 2022Review
- TP53 mutations in functional corticotroph tumors are linked to invasion and worse clinical outcome.Acta neuropathologica communications · 2022Article
- Genetic Basis of ACTH-Secreting Adenomas.International journal of molecular sciences · 2022Review
- Responsiveness to DDAVP in Cushing's disease is associated with USP8 mutations through enhancing AVPR1B promoter activity.Pituitary · 2022Article
- P720R USP8 Mutation Is Associated with a Better Responsiveness to Pasireotide in ACTH-Secreting PitNETs.Cancers · 2022Article
- Quantitative Ubiquitinomics Revealed Abnormal Ubiquitinated ATP7A Involved in Down-Regulation of ACTH in Silent Corticotroph Adenomas.Frontiers in endocrinology · 2022Article
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9 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundSomatic mutations in the ubiquitin-specific protease 8 (USP8) gene have recently been shown to occur in ACTH-secreting pituitary adenomas, thus calling attention to the ubiquitin system in corticotrope adenomas.
objectivesAssess the consequences of USP8 mutations and establish the role of ubiquitin on ACTH turnover in human ACTH-secreting pituitary adenomas.
methodsUSP8 mutation status was established in 126 ACTH-secreting adenomas. Differences in ACTH secretion and POMC expression from adenoma primary cultures and in microarray gene expression profiles from archival specimens were sought according to USP8 sequence. Ubiquitin/ACTH coimmunoprecipitation and incubation with MG132, a proteasome inhibitor, were performed in order to establish whether ubiquitin plays a role in POMC/ACTH degradation in corticotrope adenomas.
resultsUSP8 mutations were identified in 29 adenomas (23%). Adenomas presenting USP8 mutations secreted greater amounts of ACTH and expressed POMC at higher levels compared to USP wild-type specimens. USP8 mutant adenomas were also more sensitive to modulation by CRH and dexamethasone in vitro. At microarray analysis, genes associated with endosomal protein degradation and membrane components were downregulated in USP8 mutant adenomas as were AVPR1B, IL11RA, and PITX2. Inhibition of the ubiquitin-proteasome pathway increased ACTH secretion and POMC itself proved a target of ubiquitylation, independently of USP8 sequence status.
conclusionsOur study has shown that USP8 mutant ACTH-secreting adenomas present a more "typical" corticotrope phenotype and reduced expression of several genes associated with protein degradation. Further, ubiquitylation is directly involved in intracellular ACTH turnover, suggesting that the ubiquitin-proteasome system may represent a target for treatment of human ACTH-secreting adenomas.
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