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Genes regulated by UCHL1 in ovarian cancer cells

ABSTRACT: UCHL1 is related to apoptosis and proliferation in cancers and we sought to identify genes regulated by UCHL1

ORGANISM(S): Homo sapiens

PROVIDER: GSE43884 | GEO | 2013/01/30

SECONDARY ACCESSION(S): PRJNA188065

REPOSITORIES: GEO

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Genes regulated by UCHL1 in ovarian cancer cells

Project description:UCHL1 is related to apoptosis and proliferation in cancers and we sought to identify genes regulated by UCHL1 UCHL1 was knocked down in A2780 (A2780-shUCHL1). A2780-shUCHL1 and A2780-control were cultured in RPMI and total RNA was extracted and hybridizated on Affymetrix.GeneChip.HG-U133_Plus_2

2013-01-30 | E-GEOD-43884 | biostudies-arrayexpress

Differential gene expression in UCHL1 silenced ovarian cancer cells

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Differential gene expression in UCHL1 silenced ovarian cancer cells

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Ubiquitin C-terminal hydrolase isozyme L1 (UCHL1) is associated with shelterin complex at interstitial telomeric sites

Project description:Ubiquitin C-terminal hydrolase isozyme L1 (UCHL1) is primarily expressed in neuronal cells and neuroendocrine cells. It is a multifunctional protein involved in deubiquitination, ubiquitination, and ubiquitin homeostasis. UCHL1 has been associated with various diseases, including many cancers, but its specific roles are disputed and still generally undetermined. Herein, we demonstrate that UCHL1 is associated with genomic DNA in certain prostate cancer cell lines, including DU 145 cells derived from a brain metastatic site, and in HEK293T embryonic kidney cells with a neuronal lineage. Chromatin immunoprecipitation and sequencing revealed that UCHL1 localizes to TTAGGG repeats at telomeres and interstitial telomeric sequences, as do TRF1 and TRF2, components of the shelterin complex. A weak or transient interaction between UCHL1 and the shelterin complex was confirmed by immunoprecipitation and proximity ligation assays. UCHL1 and TERF2IP, also a component of the shelterin complex, were bound to the nuclear scaffold. UCHL1 may play a role in regulating gene expression by affecting the stabilization of the shelterin proteins or influencing nuclear targeting. As several shelterin proteins (TRF1, TRF2, POT1 and TERF2IP) are ubiquitinated, UCHL1 may have a role in regulating the stability of these proteins. UCHL1 may also regulate the nuclear location of shelterin-associated genomic regions.

2018-02-23 | GSE97111 | GEO

The impact of transgenic Uchl1 on gene expression in germinal center B-cells from ImHABCL6 mice

2016-01-12 | GSE76706 | GEO

The impact of transgenic Uchl1 on gene expression in germinal center B-cells from ImHABCL6 mice

Project description:This study seeks to understand the mechanisms behind enhanced lymphomagenesis observed in ImHABCL6/Uchl1 mice compared with ImHABCL6 alone. As the lymphomas arise from germinal center (GC) B-cells, we reasoned that transgenic Uchl1 altered the gene expression patterns in GC B-cells from these animals. We therefore isolated pre-malignant GC B-cells and examined the gene expression patterns to identify pathways affected by the addition of Uchl1. Germinal center B-cells were isolated from from the spleens of ImHABCL6 and ImHABCL6/Uchl1 mutant mice (n= 3 each) after immunization with sheep red blood cells. RNA was extracted and hybridized to affymetrix mouse 430 2.0 arrays.

2016-01-12 | E-GEOD-76706 | biostudies-arrayexpress

Analysis of UCHL1 knockout in brain

Project description:We analyzed the brain of 5 day old mice with homozygous and heterozygous brain specific UCHL1 knockout using nLC-MS/MS.

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Discovery of a potent and selective covalent inhibitor and activity-based probe for UCHL1, with anti-fibrotic activity

Project description:Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme (DUB) that is very highly expressed in human brain. UCHL1 has been proposed as a potential therapeutic target in neurodegeneration, cancer, and liver and lung fibrosis, however bona fide molecular functions of UCHL1 are yet to be elucidated. Herein we characterize a potent and selective inhibitor and activity-based probe (IMP-1710) for UCHL1 based on a covalent inhibitor scaffold, and its application to identify and quantify target proteins in intact human cells. IMP-1710 stereoselectively labels the catalytic cysteine of UCHL1 at low nanomolar concentration, and we show that a previously claimed UCHL1 inhibitor (LDN-57444) fails to engage UCHL1 in cells. We further demonstrate that potent UCHL1 inhibitors selectively block pro-fibrotic responses in a cellular model of idiopathic pulmonary fibrosis (IPF), supporting a potential therapeutic role for UCHL1 inhibition.

2020-11-12 | PXD015825 | Pride

UCHL1 aggravates skin fibrosis through an IGF-1-induced AKT/mTOR/ HIF-1α pathway in keloid

Project description:To investigate the function of UCHL1 in keloids, we established primary dermal fibroblasts in which the target gene has been overexpressed by lentiviral transfection.

2022-11-21 | GSE211150 | GEO

Small-Molecule Activity-Based Probe for Monitoring Ubiquitin 2 C‑Terminal Hydrolase (UCHL1) Activity in Live Cells and Zebrafish 3 Embryos

Project description:Many reagents have emerged to study the function of specific enzymes in vitro. On the other hand, target specific reagents are scarce or need improvement, allowing investigations of the function of individual enzymes in their native cellular context. Here we report the development of a target-selective fluorescent small-molecule activity-based DUB probe that is active in live cells and an in vivo animal model. The probe labels active ubiquitin carboxy-terminal hydrolase L1 (UCHL1), also known as neuron-specific protein PGP9.5 (PGP9.5) and Parkinson disease 5 (PARK5), a DUB active in neurons that constitutes 1 to 2% of the total brain protein. UCHL1 variants have been linked with neurodegenerative disorders Parkinson’s and Alzheimer’s diseases. In addition, high levels of UCHL1 also correlate often with cancer and especially metastasis. The function of UCHL1 activity or its role in cancer and neurodegenerative disease is poorly understood and few UCHL1-specific activity tools exist. We show that the reagents reported here are specific to UCHL1 over all other DUBs detectable by competitive activity-based protein profiling and by mass spectrometry. Our cell-penetrable probe, which contains a cyanimide reactive moiety, binds to the active-site cysteine residue of UCHL1 in an activity-dependent manner. Its use is demonstrated by the fluorescent labeling of active UCHL1 both in vitro and in live cells. We furthermore show that this probe can selectively and spatiotemporally report UCHL1 activity during the development of zebrafish embryos. Our results indicate that our probe has potential applications as a diagnostic tool for diseases with perturbed UCHL1 activity.

2020-09-18 | PXD021557 | Pride

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