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Deubiquitination

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https://www.readbyqxmd.com/read/28216291/ovarian-tumor-domain-containing-protein-1-deubiquitinates-and-stabilizes-p53
#1
Shudong Piao, Han Zhong Pei, Bin Huang, Suk-Hwan Baek
Ubiquitination and deubiquitination pathways play important roles in the regulation of p53 stability and activity. p53 is ubiquitinated and destabilized by E3 ubiquitin ligases and is deubiquitinated and stabilized by deubiquitinases (DUBs). We screened ovarian tumor (OTU) subfamily proteins to identify novel DUBs that stabilized p53. OTU domain-containing protein 1 (OTUD1) is a DUB belonging to the OTU family; however, its substrates and its role in cells are unknown. Here, we used an overexpression and knockdown system to show that OTUD1 is a novel regulator of p53 stability...
February 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28216017/usp7-inhibitor-p5091-inhibits-wnt-signaling-and-colorectal-tumor-growth
#2
An Tao, Gong Yaxiao, Li Xue, Kong Lingmei, Ma Pengcheng, Gong Liang, Zhu Huifang, Yu Chunlei, Liu Jianmei, Zhou Hongyu, Mao Bingyu, Li Yan
Aberrant activation of Wnt/β-catenin signaling is closely associated with the development of various human cancers, especially colorectal cancers (CRC). The ubiquitin proteasome system (UPS) is essential in the regulation of Wnt signaling and inhibitors targeting the UPS could have great potential in CRC therapy. Ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, plays a significant role in neoplastic diseases due to its well-known function of regulating the MDM2-p53 complex. Inspired by our recent study identifying the positive role of USP7 in the Wnt signaling, we report here that USP7 is overexpressed in colorectal carcinoma cell lines and tissues, which is closely related with the poor prognosis...
February 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28203236/the-deubiquitinating-enzyme-cylindromatosis-dampens-cd8-t-cell-responses-and-is-a-critical-factor-for-experimental-cerebral-malaria-and-blood-brain-barrier-damage
#3
Ursula Schmid, Werner Stenzel, Josephin Koschel, Maria Raptaki, Xu Wang, Michael Naumann, Kai Matuschewski, Dirk Schlüter, Gopala Nishanth
Cerebral malaria is a severe complication of human malaria and may lead to death of Plasmodium falciparum-infected individuals. Cerebral malaria is associated with sequestration of parasitized red blood cells within the cerebral microvasculature resulting in damage of the blood-brain barrier and brain pathology. Although CD8(+) T cells have been implicated in the development of murine experimental cerebral malaria (ECM), several other studies have shown that CD8(+) T cells confer protection against blood-stage infections...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28198701/deubiquitination-in-cancer-stem-cells
#4
Julia M Fraile, Diana Campos-Iglesias, José M P Freije
No abstract text is available yet for this article.
February 12, 2017: Aging
https://www.readbyqxmd.com/read/28198400/ubiquitin-c-terminal-hydrolase37-regulates-tcf7-dna-binding-for-the-activation-of-wnt-signalling
#5
Wonhee Han, Hyeyoon Lee, Jin-Kwan Han
The Tcf/Lef family of transcription factors mediates the Wnt/β-catenin pathway that is involved in a wide range of biological processes, including vertebrate embryogenesis and diverse pathogenesis. Post-translational modifications, including phosphorylation, sumoylation and acetylation, are known to be important for the regulation of Tcf/Lef proteins. However, the importance of ubiquitination and ubiquitin-mediated regulatory mechanisms for Tcf/Lef activity are still unclear. Here, we newly show that ubiquitin C-terminal hydrolase 37 (Uch37), a deubiquitinase, interacts with Tcf7 (formerly named Tcf1) to activate Wnt signalling...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198367/usp9x-regulates-ets-1-ubiquitination-and-stability-to-control-nras-expression-and-tumorigenicity-in-melanoma
#6
Harish Potu, Luke F Peterson, Malathi Kandarpa, Anupama Pal, Hanshi Sun, Alison Durham, Paul W Harms, Peter C Hollenhorst, Ugur Eskiocak, Moshe Talpaz, Nicholas J Donato
ETS transcription factors are commonly deregulated in cancer by chromosomal translocation, overexpression or post-translational modification to induce gene expression programs essential in tumorigenicity. Targeted destruction of these proteins may have therapeutic impact. Here we report that Ets-1 destruction is regulated by the deubiquitinating enzyme, Usp9x, and has major impact on the tumorigenic program of metastatic melanoma. Ets-1 deubiquitination blocks its proteasomal destruction and enhances tumorigenicity, which could be reversed by Usp9x knockdown or inhibition...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28196907/acetylation-dependent-regulation-of-mdm2-e3-ligase-activity-dictates-its-oncogenic-function
#7
Naoe T Nihira, Kohei Ogura, Kouhei Shimizu, Brian J North, Jinfang Zhang, Daming Gao, Hiroyuki Inuzuka, Wenyi Wei
Abnormal activation of the oncogenic E3 ubiquitin ligase murine double minute 2 (MDM2) is frequently observed in human cancers. By ubiquitinating the tumor suppressor p53 protein, which leads to its proteasome-mediated destruction, MDM2 limits the tumor-suppressing activity of p53. On the other hand, by ubiquitinating itself, MDM2 targets itself for destruction and promotes the p53 tumor suppressor pathway, a process that can be antagonized by the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP)...
February 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28188342/the-equilibrium-of-ubiquitination-and-deubiquitination-at-plk1-regulates-sister-chromatid-separation
#8
REVIEW
Junjun Liu, Chuanmao Zhang
PLK1 regulates almost every aspect of mitotic events, including mitotic entry, spindle assembly, chromosome alignment, sister chromatid segregation, metaphase-anaphase transition, cytokinesis, etc. In regulating the chromosome alignment and sister chromatid segregation, PLK1 has to be localized to and removed from kinetochores at the right times, and the underlying mechanism that regulates PLK1 both spatially and temporally only became clearer recently. It has been found that deubiquitination and ubiquitination of PLK1 are responsible for its localization to and dissociation from the kinetochores, respectively...
February 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28177072/the-evolution-and-functional-diversification-of-the-deubiquitinating-enzyme-superfamily
#9
Caitlyn Vlasschaert, David Cook, Xuhua Xia, Douglas A Gray
No abstract text is available yet for this article.
February 8, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28167606/the-deubiquitinating-enzyme-usp20-regulates-erk3-stability-and-biological-activity
#10
Simon Mathien, Paul Déléris, Mathilde Soulez, Laure Voisin, Sylvain Meloche
Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein (MAP) kinase whose regulatory mechanisms and biological functions remain superficially understood. Contrary to most protein kinases, ERK3 is a highly unstable protein that is subject to dynamic regulation by the ubiquitin-proteasome system. However, the effectors that control ERK3 ubiquitination and degradation are unknown. In this study, we carried out an unbiased functional loss-of-function screen of the human deubiquitinating enzyme (DUB) family and identified ubiquitin-specific protease 20 (USP20) as a novel ERK3 regulator...
February 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28160502/deubiquitinating-enzyme-usp22-positively-regulates-c-myc-stability-and-tumorigenic-activity-in-mammalian-and-breast-cancer-cells
#11
Dongyeon Kim, Ahyoung Hong, Hye In Park, Woo Hyun Shin, Lang Yoo, Seo Jeong Jeon, Kwang Chul Chung
The proto-oncogene c-Myc has a pivotal function in growth control, differentiation and apoptosis and is frequently affected in human cancer, including breast cancer. Ubiquitin-specific protease 22 (USP22), a member of the USP family of deubiquitinating enzymes (DUBs), mediates deubiquitination of target proteins, including histone H2B and H2A, telomeric repeat binding factor 1, and cyclin B1. USP22 is also a component of the mammalian SAGA transcriptional co-activating complex. In this study, we explored the functional role of USP22 in modulating c-Myc stability and its physiological relevance in breast cancer progression...
February 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28153028/il-1%C3%AE-impairs-retrograde-flow-of-bdnf-signaling-by-attenuating-endosome-trafficking
#12
Anthony J Carlos, Liqi Tong, G Aleph Prieto, Carl W Cotman
BACKGROUND: Pro-inflammatory cytokines accumulate in the brain with age and Alzheimer's disease and can impair neuron health and cognitive function. Brain-derived neurotrophic factor (BDNF) is a key neurotrophin that supports neuron health, function, and synaptic plasticity. The pro-inflammatory cytokine interleukin-1β (IL-1β) impairs BDNF signaling but whether it affects BDNF signaling endosome trafficking has not been studied. METHODS: This study uses an in vitro approach in primary hippocampal neurons to evaluate the effect of IL-1β on BDNF signaling endosome trafficking...
February 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28151478/proteasome-associated-deubiquitinase-ubiquitin-specific-protease-14-regulates-prostate-cancer-proliferation-by-deubiquitinating-and-stabilizing-androgen-receptor
#13
Yuning Liao, Ningning Liu, Xianliang Hua, Jianyu Cai, Xiaohong Xia, Xuejun Wang, Hongbiao Huang, Jinbao Liu
Androgen receptor (AR) is frequently over-expressed and plays a critical role in the growth and progression of human prostate cancer. The therapy attempting to target AR signalling was established in decades ago but the treatment of prostate cancer is far from being satisfactory. The assignable cause is that our understanding of the mechanism of AR regulation and re-activation remains incomplete. Increasing evidence suggests that deubiquitinases are involved in the regulation of cancer development and progression but the specific underlying mechanism often is not elucidated...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28139865/silencing-of-otub1-inhibits-migration-of-human-glioma-cells-in-vitro
#14
Li Xu, Jinquan Li, Zhen Bao, Peng Xu, Hao Chang, Jingjing Wu, Yuanqi Bei, Liuwan Xia, Peizhang Wu, Ke Yan, Bing Lu, Gang Cui
OTU domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) protein, a deubiquitinating enzyme (DUB) which belongs to the ovarian tumor (OTU) family, was reported to be associated with the development of various malignancies. However, the potential function of OTUB1 in human gliomas was still unclear. In this study, we sought to investigate the function of OTUB1 in the pathological process of gliomas and analyze its related clinical significance. Western blot and immunohistochemistry analyses demonstrated that OTUB1 was overexpressed in glioma tissues, and statistical analysis suggested the expression level of OTUB1 was significantly correlated with the WHO grades of human gliomas (P < 0...
January 31, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28137592/usp7-promotes-medulloblastoma-cell-survival-and-metastasis-by-activating-shh-pathway
#15
Meixiao Zhan, Xiaohan Sun, Jinxiao Liu, Yan Li, Yong Li, Xu He, Zizhang Zhou, Ligong Lu
The ubiquitin-specific protease Usp7 plays roles in multiple cellular processes through deubiquitinating and stabilizing numerous substrates, including P53, Pten and Gli. Aberrant Usp7 activity has been implicated in many disorders and tumorigenesis, making it as a potential target for therapeutic intervention. Although it is clear that Usp7 is involved in many types of cancer, its role in regulating medulloblastoma (MB) is still unknown. In this study, we show that knockdown of Usp7 inhibits the proliferation and migration of MB cells, while Usp7 overexpression exerts an opposite effect...
January 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28134560/chloroquine-attenuates-lipopolysaccharide-induced-inflammatory-responses-through-upregulation-of-usp25
#16
Changyu Ding, Fangfang Li, Yupeng Long, Jiang Zheng
Lipopolysaccharide (LPS) is a key pathogenic factor in sepsis, and its recognition by toll-like receptor 4 (TLR4) can activate two district signaling pathways, leading to activation of transcription factors including NF-κB and interferon regulatory factor 3 (IRF3). Chloroquine (CQ) has been shown to affect LPS-TLR4 colocalization and inhibit both MyD88-dependent and TRAM/TRIF-dependent pathways, though the mechanism involved is still poorly understood. Here, we found that the ubiquitin-proteasome system might be involved in this process...
November 30, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28132030/usp15-regulates-dynamic-protein-protein-interactions-of-the-spliceosome-through-deubiquitination-of-prp31
#17
Tanuza Das, Joon Kyu Park, Jinyoung Park, Eunji Kim, Michael Rape, Eunice EunKyeong Kim, Eun Joo Song
No abstract text is available yet for this article.
January 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28115216/mysm1-deficiency-genotoxic-stress-associated-bone-marrow-failure-and-developmental-aberrations
#18
Ehsan Bahrami, Maximilian Witzel, Tomas Racek, Jacek Puchałka, Sebastian Hollizeck, Naschla Greif-Kohistani, Daniel Kotlarz, Hans-Peter Horny, Regina Feederle, Heinrich Schmidt, Roya Sherkat, Doris Steinemann, Gudrun Göhring, Brigitte Schlegelbeger, Michael H Albert, Waleed Al-Herz, Christoph Klein
BACKGROUND: Myb-Like, SWIRM and MPN domains 1 (MYSM1) is a transcriptional regulator mediating histone deubiquitination. Its role in human immunity and hematopoiesis is poorly understood. OBJECTIVES: To investigate the clinical, cellular and molecular features in two siblings presenting with progressive bone marrow failure, immunodeficiency and developmental aberrations. METHODS: We performed genome-wide homozygosity mapping, whole-exome sequencing (WES) and Sanger sequencing, immunophenotyping studies as well as analysis of genotoxic stress responses...
January 20, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28105162/ubiquitin-specific-protease-21-upregulation-in-breast-cancer-promotes-cell-tumorigenic-capability-and-is-associated-with-the-nod-like-receptor-signaling-pathway
#19
Liang Peng, Yi Hu, Demeng Chen, Ruixia Linghu, Yingzhe Wang, Xiaoxue Kou, Junlan Yang, Shunchang Jiao
Ubiquitination and deubiquitination have emerged as critical regulators in cancer. In the present study, the expression pattern of 50 ubiquitin-specific proteases (USPs) was summarized in breast cancer using a bioinformatics approach, and USP21 was identified as the most altered gene in breast cancer. In particular, expression of USP21 in triple negative breast cancer (TNBC) cell lines was greater compared with other subtypes of breast cancer. Knockdown of USP21 in TNBC cells inhibited cell proliferation, migration and invasion...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28096485/murine-cytomegalovirus-deubiquitinase-regulates-viral-chemokine-levels-to-control-inflammation-and-pathogenesis
#20
Adam T Hilterbrand, Daniel R Boutz, Edward M Marcotte, Jason W Upton
: Maintaining control over inflammatory processes represents a paradox for viral pathogens. Although many viruses induce host inflammatory responses to facilitate infection, control is necessary to avoid overactivation. One way is through the manipulation of proinflammatory chemokine levels, both host and viral. Murine cytomegalovirus (MCMV), a model betaherpesvirus, encodes a viral C-C chemokine, MCK2, which promotes host inflammatory responses and incorporates into virions to facilitate viral dissemination...
January 17, 2017: MBio
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