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Mutations in the deubiquitinase gene USP8 cause Cushing's disease

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Mutations in the deubiquitinase gene USP8 cause Cushing's disease. / Reincke, Martin; Sbiera, Silviu; Hayakawa, Akira; Theodoropoulou, Marily; Osswald, Andrea; Beuschlein, Felix; Meitinger, Thomas; Mizuno-Yamasaki, Emi; Kawaguchi, Kohei; Saeki, Yasushi; Tanaka, Keiji; Wieland, Thomas; Graf, Elisabeth; Saeger, Wolfgang; Ronchi, Cristina L; Allolio, Bruno; Buchfelder, Michael; Strom, Tim M; Fassnacht, Martin; Komada, Masayuki.

in: NAT GENET, Jahrgang 47, Nr. 1, 01.2015, S. 31-8.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Reincke, M, Sbiera, S, Hayakawa, A, Theodoropoulou, M, Osswald, A, Beuschlein, F, Meitinger, T, Mizuno-Yamasaki, E, Kawaguchi, K, Saeki, Y, Tanaka, K, Wieland, T, Graf, E, Saeger, W, Ronchi, CL, Allolio, B, Buchfelder, M, Strom, TM, Fassnacht, M & Komada, M 2015, 'Mutations in the deubiquitinase gene USP8 cause Cushing's disease', NAT GENET, Jg. 47, Nr. 1, S. 31-8. https://doi.org/10.1038/ng.3166

APA

Reincke, M., Sbiera, S., Hayakawa, A., Theodoropoulou, M., Osswald, A., Beuschlein, F., Meitinger, T., Mizuno-Yamasaki, E., Kawaguchi, K., Saeki, Y., Tanaka, K., Wieland, T., Graf, E., Saeger, W., Ronchi, C. L., Allolio, B., Buchfelder, M., Strom, T. M., Fassnacht, M., & Komada, M. (2015). Mutations in the deubiquitinase gene USP8 cause Cushing's disease. NAT GENET, 47(1), 31-8. https://doi.org/10.1038/ng.3166

Vancouver

Reincke M, Sbiera S, Hayakawa A, Theodoropoulou M, Osswald A, Beuschlein F et al. Mutations in the deubiquitinase gene USP8 cause Cushing's disease. NAT GENET. 2015 Jan;47(1):31-8. https://doi.org/10.1038/ng.3166

Bibtex

@article{cb248de0533549319f7ef160f7e27776,
title = "Mutations in the deubiquitinase gene USP8 cause Cushing's disease",
abstract = "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.",
keywords = "14-3-3 Proteins, ACTH-Secreting Pituitary Adenoma, Adenoma, Adrenocorticotropic Hormone, Amino Acid Sequence, Animals, COS Cells, Cercopithecus aethiops, Endopeptidases, Endosomal Sorting Complexes Required for Transport, Exome, Gene Expression Regulation, Neoplastic, Humans, Molecular Sequence Data, Mutation, Neoplasm Proteins, Pituitary ACTH Hypersecretion, Pituitary Neoplasms, Pro-Opiomelanocortin, Receptor, Epidermal Growth Factor, Sequence Alignment, Sequence Homology, Amino Acid, Ubiquitin Thiolesterase",
author = "Martin Reincke and Silviu Sbiera and Akira Hayakawa and Marily Theodoropoulou and Andrea Osswald and Felix Beuschlein and Thomas Meitinger and Emi Mizuno-Yamasaki and Kohei Kawaguchi and Yasushi Saeki and Keiji Tanaka and Thomas Wieland and Elisabeth Graf and Wolfgang Saeger and Ronchi, {Cristina L} and Bruno Allolio and Michael Buchfelder and Strom, {Tim M} and Martin Fassnacht and Masayuki Komada",
year = "2015",
month = jan,
doi = "10.1038/ng.3166",
language = "English",
volume = "47",
pages = "31--8",
journal = "NAT GENET",
issn = "1061-4036",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Mutations in the deubiquitinase gene USP8 cause Cushing's disease

AU - Reincke, Martin

AU - Sbiera, Silviu

AU - Hayakawa, Akira

AU - Theodoropoulou, Marily

AU - Osswald, Andrea

AU - Beuschlein, Felix

AU - Meitinger, Thomas

AU - Mizuno-Yamasaki, Emi

AU - Kawaguchi, Kohei

AU - Saeki, Yasushi

AU - Tanaka, Keiji

AU - Wieland, Thomas

AU - Graf, Elisabeth

AU - Saeger, Wolfgang

AU - Ronchi, Cristina L

AU - Allolio, Bruno

AU - Buchfelder, Michael

AU - Strom, Tim M

AU - Fassnacht, Martin

AU - Komada, Masayuki

PY - 2015/1

Y1 - 2015/1

N2 - 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.

AB - 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.

KW - 14-3-3 Proteins

KW - ACTH-Secreting Pituitary Adenoma

KW - Adenoma

KW - Adrenocorticotropic Hormone

KW - Amino Acid Sequence

KW - Animals

KW - COS Cells

KW - Cercopithecus aethiops

KW - Endopeptidases

KW - Endosomal Sorting Complexes Required for Transport

KW - Exome

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Molecular Sequence Data

KW - Mutation

KW - Neoplasm Proteins

KW - Pituitary ACTH Hypersecretion

KW - Pituitary Neoplasms

KW - Pro-Opiomelanocortin

KW - Receptor, Epidermal Growth Factor

KW - Sequence Alignment

KW - Sequence Homology, Amino Acid

KW - Ubiquitin Thiolesterase

U2 - 10.1038/ng.3166

DO - 10.1038/ng.3166

M3 - SCORING: Journal article

C2 - 25485838

VL - 47

SP - 31

EP - 38

JO - NAT GENET

JF - NAT GENET

SN - 1061-4036

IS - 1

ER -