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ATXN7L3 And ENY2 Coordinate Activity Of Multiple H2B Deubiquitinases Important For Cellular Proliferation And Tumor Growth

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE79967 | GEO | 2016/04/06

SECONDARY ACCESSION(S): PRJNA317530

REPOSITORIES: GEO

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ATXN7L3 And ENY2 Coordinate Activity Of Multiple H2B Deubiquitinases Important For Cellular Proliferation And Tumor Growth

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-04-06 | E-GEOD-79967 | biostudies-arrayexpress

ATXN7L3 and ENY2 Coordinate Activity of Multiple H2B Deubiquitinases Important for Cellular Proliferation and Tumor Growth.

Project description:Histone H2B monoubiquitination (H2Bub1) is centrally involved in gene regulation. The deubiquitination module (DUBm) of the SAGA complex is a major regulator of global H2Bub1 levels, and components of this DUBm are linked to both neurodegenerative diseases and cancer. Unexpectedly, we find that ablation of USP22, the enzymatic center of the DUBm, leads to a reduction, rather than an increase, in global H2bub1 levels. In contrast, depletion of non-enzymatic components, ATXN7L3 or ENY2, results in increased H2Bub1. These observations led us to discover two H2Bub1 DUBs, USP27X and USP51, which function independently of SAGA and compete with USP22 for ATXN7L3 and ENY2 for activity. Like USP22, USP51 and USP27X are required for normal cell proliferation, and their depletion suppresses tumor growth. Our results reveal that ATXN7L3 and ENY2 orchestrate activities of multiple deubiquitinating enzymes and that imbalances in these activities likely potentiate human diseases including cancer.

| S-EPMC4874879 | biostudies-literature

ATXN7L3 And ENY2 Coordinate Activity Of Multiple H2B Deubiquitinases Important For Cellular Proliferation And Tumor Growth [RNA-Seq]

Project description:We report that H2B deubiquitinating enzymes USP22, USP27x and USP51 have both unique and overlapping target loci. Comparing gene expression profiles of MCF7 cells stably expressing shRNA targeting either USP22, USP27X or USP51 and cells expressing non-targeting shRNA.

2016-04-06 | E-GEOD-79861 | biostudies-arrayexpress

ATXN7L3 And ENY2 Coordinate Activity Of Multiple H2B Deubiquitinases Important For Cellular Proliferation And Tumor Growth [ChIP-Seq]

Project description:We report that the H2B deubiquitinating enzymes USP22, USP27x and USP51 have both unique and overlapping target loci. Comparing H2Bb1 (K120) distribution profiles of MCF7 cells stably expressing shRNA targeting ATXN7L3, USP22, USP27X or USP51 and cells expressing non-targeting shRNA.

2016-04-06 | E-GEOD-79966 | biostudies-arrayexpress

ATXN7L3 And ENY2 Coordinate Activity Of Multiple H2B Deubiquitinases Important For Cellular Proliferation And Tumor Growth [ChIP-Seq]

Project description:We report that the H2B deubiquitinating enzymes USP22, USP27x and USP51 have both unique and overlapping target loci.

2016-04-06 | GSE79966 | GEO

ATXN7L3 And ENY2 Coordinate Activity Of Multiple H2B Deubiquitinases Important For Cellular Proliferation And Tumor Growth [RNA-Seq]

Project description:We report that H2B deubiquitinating enzymes USP22, USP27x and USP51 have both unique and overlapping target loci.

2016-04-06 | GSE79861 | GEO

ATXN7L3 And ENY2 Coordinate Activity Of Multiple H2B Deubiquitinases Important For Cellular Proliferation And Tumor Growth

Project description:ATXN7L3 And ENY2 Coordinate Activity Of Multiple H2B Deubiquitinases Important For Cellular Proliferation And Tumor Growth

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Coordinate β-adrenergic inhibition of mitochondrial activity and angiogenesis arrest tumor growth.

Project description:Mitochondrial metabolism has emerged as a promising target against the mechanisms of tumor growth. Herein, we have screened an FDA-approved library to identify drugs that inhibit mitochondrial respiration. The β1-blocker nebivolol specifically hinders oxidative phosphorylation in cancer cells by concertedly inhibiting Complex I and ATP synthase activities. Complex I inhibition is mediated by interfering the phosphorylation of NDUFS7. Inhibition of the ATP synthase is exerted by the overexpression and binding of the ATPase Inhibitory Factor 1 (IF1) to the enzyme. Remarkably, nebivolol also arrests tumor angiogenesis by arresting endothelial cell proliferation. Altogether, targeting mitochondria and angiogenesis triggers a metabolic and oxidative stress crisis that restricts the growth of colon and breast carcinomas. Nebivolol holds great promise to be repurposed for the treatment of cancer patients.

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Coordinate β-adrenergic inhibition of mitochondrial activity and angiogenesis arrest tumor growth

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mTORC1 regulates PTHrP to coordinate chondrocyte growth, proliferation and differentiation.

Project description:Precise coordination of cell growth, proliferation and differentiation is essential for the development of multicellular organisms. Here, we report that although the mechanistic target of rapamycin complex 1 (mTORC1) activity is required for chondrocyte growth and proliferation, its inactivation is essential for chondrocyte differentiation. Hyperactivation of mTORC1 via TSC1 gene deletion in chondrocytes causes uncoupling of the normal proliferation and differentiation programme within the growth plate, resulting in uncontrolled cell proliferation, and blockage of differentiation and chondrodysplasia in mice. Rapamycin promotes chondrocyte differentiation and restores these defects in mutant mice. Mechanistically, mTORC1 downstream kinase S6K1 interacts with and phosphorylates Gli2, and releases Gli2 from SuFu binding, resulting in nuclear translocation of Gli2 and transcription of parathyroid hormone-related peptide (PTHrP), a key regulator of bone development. Our findings demonstrate that dynamically controlled mTORC1 activity is crucial to coordinate chondrocyte proliferation and differentiation partially through regulating Gli2/PTHrP during endochondral bone development.

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