Read by QxMD icon Read


Julia M Fraile, Diana Campos-Iglesias, Francisco Rodríguez, Yaiza Español, José M P Freije
Ubiquitin-Specific Proteases (USPs) are deubiquitinating enzymes frequently deregulated in human malignancies. Here, we show that USP54 is overexpressed in intestinal stem cells and demonstrate that its downregulation in colorectal carcinoma cells impedes tumorigenesis. We have generated mutant mice deficient for this deubiquitinase, which are viable and fertile, and protected against chemically-induced colorectal carcinoma. Furthermore, we show that USP54 is upregulated in human colon cancer and associates with poor prognosis...
October 19, 2016: Oncotarget
Heba M Ismail, Athanasios Didangelos, Tonia L Vincent, Jeremy Saklatvala
Objectives Mechanical injury to cartilage predisposes to osteoarthritis (OA). Wounding the articular cartilage surface causes rapid activation of MAP kinases and NFκB mimicking the response to inflammatory cytokines. Here, we identify the upstream signalling mechanisms involved. Methods Cartilage was injured by dissecting it from the articular surface of porcine metacarpophalangeal joints (MCP) or by avulsing murine proximal femoral epiphyses. Protein phosphorylation was assayed by Western blotting of cartilage lysates...
October 21, 2016: Arthritis & Rheumatology
Guoqiang Ma, Shuang Li, Yuhong Han, Shuangxi Li, Tao Yue, Bing Wang, Jin Jiang
Hedgehog (Hh) signaling plays a central role in development and diseases. Hh activates its signal transducer and GPCR-family protein Smoothened (Smo) by inducing Smo phosphorylation, but whether Smo is activated through other post-translational modifications remains unexplored. Here we show that sumoylation acts in parallel with phosphorylation to promote Smo cell-surface expression and Hh signaling. We find that Hh stimulates Smo sumoylation by dissociating it from a desumoylation enzyme Ulp1. Sumoylation of Smo in turn recruits a deubiquitinase UBPY/USP8 to antagonize Smo ubiquitination and degradation, leading to its cell-surface accumulation and elevated Hh pathway activity...
October 7, 2016: Developmental Cell
Tycho E T Mevissen, Yogesh Kulathu, Monique P C Mulder, Paul P Geurink, Sarah L Maslen, Malte Gersch, Paul R Elliott, John E Burke, Bianca D M van Tol, Masato Akutsu, Farid El Oualid, Masato Kawasaki, Stefan M V Freund, Huib Ovaa, David Komander
The post-translational modification of proteins with polyubiquitin regulates virtually all aspects of cell biology. Eight distinct chain linkage types co-exist in polyubiquitin and are independently regulated in cells. This 'ubiquitin code' determines the fate of the modified protein. Deubiquitinating enzymes of the ovarian tumour (OTU) family regulate cellular signalling by targeting distinct linkage types within polyubiquitin, and understanding their mechanisms of linkage specificity gives fundamental insights into the ubiquitin system...
October 12, 2016: Nature
Arno F Alpi, Viduth Chaugule, Helen Walden
Ubiquitin signalling is a fundamental eukaryotic regulatory system, controlling diverse cellular functions. A cascade of E1, E2, and E3 enzymes is required for assembly of distinct signals, whereas an array of deubiquitinases and ubiquitin-binding modules edit, remove, and translate the signals. In the centre of this cascade sits the E2-conjugating enzyme, relaying activated ubiquitin from the E1 activating enzyme to the substrate, usually via an E3 ubiquitin ligase. Many disease states are associated with dysfunction of ubiquitin signalling, with the E3s being a particular focus...
October 15, 2016: Biochemical Journal
Nancy N Fang, Mang Zhu, Amalia Rose, Kuen-Phon Wu, Thibault Mayor
Elimination of misfolded proteins is crucial for proteostasis and to prevent proteinopathies. Nedd4/Rsp5 emerged as a major E3-ligase involved in multiple quality control pathways that target misfolded plasma membrane proteins, aggregated polypeptides and cytosolic heat-induced misfolded proteins for degradation. It remained unclear how in one case cytosolic heat-induced Rsp5 substrates are destined for proteasomal degradation, whereas other Rsp5 quality control substrates are otherwise directed to lysosomal degradation...
October 4, 2016: Nature Communications
Berthe Katrine Fiil, Mads Gyrd-Hansen
Ubiquitin chains assembled via the N-terminal methionine (Met1 or linear ubiquitin), conjugated by the linear ubiquitin chain assembly complex (LUBAC), participate in NF-κΒ-dependent inflammatory signaling and immune responses. A recent report in Cell finds that OTULIN, a deubiquitinase that selectively cleaves Met1-linked ubiquitin chains, is essential for restraining inflammation in vivo.
September 30, 2016: Cell Research
Mindy I Davis, Rajan Pragani, Jennifer T Fox, Min Shen, Kalindi Parmar, Emily F Gaudiano, Li Liu, Cordelle Tanega, Lauren McGee, Matthew David Hall, Crystal McKnight, Paul Shinn, Henrike Nelson, Debasish Chattopadhyay, Alan D D'Andrea, Douglas S Auld, Larry J DeLucas, Zhuyin Li, Matthew B Boxer, Anton Simeonov
Deubiquitinases are important components of the protein degradation regulatory network. We report the discovery of ML364, a small molecule inhibitor of the deubiquitinase USP2 and its use to interrogate the biology of USP2 and its putative substrate Cyclin D1. ML364 has an IC50 of 1.1 uM in a biochemical assay using an internally quenched fluorescent di-ubiquitin substrate. Direct binding of ML364 to USP2 was demonstrated using microscale thermophoresis. ML364 induced an increase in cellular Cyclin D1 degradation and caused cell-cycle arrest as shown in western blots and flow cytometry assays utilizing both mino and HCT116 cancer cell lines...
September 28, 2016: Journal of Biological Chemistry
Bindu Nanduri, Leslie A Shack, Aswathy N Rai, William B Epperson, Wes Baumgartner, Ty B Schmidt, Mariola J Edelmann
To develop a reproducible tissue lysis method that retains enzyme function for activity-based protein profiling, we compared four different methods to obtain protein extracts from bovine lung tissue: focused ultrasonication, standard sonication, mortar & pestle method, and homogenization combined with standard sonication. Focused ultrasonication and mortar & pestle methods were sufficiently effective for activity-based profiling of deubiquitinases in tissue, and focused ultrasonication also had the fastest processing time...
December 15, 2016: Analytical Biochemistry
Yu Qian, Boshi Wang, Aihui Ma, Li Zhang, Guiqin Xu, Qi Ding, Tiantian Jing, Lin Wu, Yun Liu, Zhaojuan Yang, Yongzhong Liu
Hepatitis B virus (HBV) infection is a major factor that contributes to the development of hepatocellular carcinoma (HCC). HBV X protein (HBx) has been shown to accelerate HCC progression by promoting tumour growth and metastasis. In the clinic, carboxyl-terminal truncated HBx (Ct-HBx) proteins are frequently present in HCC tumour tissues, but not in non-tumorous tissues. In this study, we analysed deubiquitinase expression profiles in cells with or without ectopic expression of the Ct-HBx proteins and observed that the expression of ubiquitin specific peptidase 16 (USP16) was substantially inhibited by Ct-HBx proteins...
2016: Scientific Reports
Shan Wang, Rahul K Kollipara, Caroline G Humphries, Shi-Hong Ma, Ryan Hutchinson, Rui Li, Javed Siddiqui, Scott A Tomlins, Ganesh V Raj, Ralf Kittler
Ets related gene (ERG) is a transcription factor that is overexpressed in 40% of prostate tumors due to a gene fusion between ERG and TMPRSS2. Because ERG functions as a driver of prostate carcinogenesis, understanding the mechanisms that influence its turnover may provide new molecular handles to target the protein. Previously, we found that ERG undergoes ubiquitination and then is deubiquitinated by USP9X in prostate cancer cells to prevent its proteasomal degradation. Here, we identify Tripartite motif-containing protein 25 (TRIM25) as the E3 ubiquitin ligase that ubiquitinates the protein prior to its degradation...
September 8, 2016: Oncotarget
Omid Tavana, Dawei Li, Chao Dai, Gonzalo Lopez, Debarshi Banerjee, Ning Kon, Chao Chen, Andrea Califano, Darrell J Yamashiro, Hongbin Sun, Wei Gu
The MYCN proto-oncogene is amplified in a number of advanced-stage human tumors, such as neuroblastomas. Similar to other members of the MYC family of oncoproteins, MYCN (also known as N-Myc) is a transcription factor, and its stability and activity are tightly controlled by ubiquitination-dependent proteasome degradation. Although numerous studies have demonstrated that N-Myc is a driver of neuroblastoma tumorigenesis, therapies that directly suppress N-Myc activity in human tumors are limited. Here we have identified ubiquitin-specific protease 7 (USP7; also known as HAUSP) as a regulator of N-Myc function in neuroblastoma...
October 2016: Nature Medicine
Ana Sofia Carvalho, Manuel S Rodríguez, Rune Matthiesen
Automatic analysis of increasingly growing literature repositories including data integration to other databases is a powerful tool to propose hypothesis that can be used to plan experiments to validate or disprove the hypothesis. Furthermore, it provides means to evaluate the redundancy of research line in comparison to the published literature. This is potentially beneficial for those developing research in a specific disease which are interested in exploring a particular pathway or set of genes/proteins...
2016: Methods in Molecular Biology
Laura D Gallego, Medini Ghodgaonkar Steger, Anton A Polyansky, Tobias Schubert, Bojan Zagrovic, Ning Zheng, Tim Clausen, Franz Herzog, Alwin Köhler
Cotranscriptional ubiquitination of histone H2B is key to gene regulation. The yeast E3 ubiquitin ligase Bre1 (human RNF20/40) pairs with the E2 ubiquitin conjugating enzyme Rad6 to monoubiquitinate H2B at Lys123. How this single lysine residue on the nucleosome core particle (NCP) is targeted by the Rad6-Bre1 machinery is unknown. Using chemical cross-linking and mass spectrometry, we identified the functional interfaces of Rad6, Bre1, and NCPs in a defined in vitro system. The Bre1 RING domain cross-links exclusively with distinct regions of histone H2B and H2A, indicating a spatial alignment of Bre1 with the NCP acidic patch...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
Wenqian Li, Boyko S Atanassov, Xianjiang Lan, Ryan D Mohan, Selene K Swanson, Aimee T Farria, Laurence Florens, Michael P Washburn, Jerry L Workman, Sharon Y R Dent
The SAGA complex contains two enzymatic modules, which house histone acetyltransferase (HAT) and deubiquitinase (DUB) activity. USP22 is the catalytic subunit of the DUB module, but two adaptor proteins, ATXN7L3 and ENY2, are necessary for DUB activity towards histone H2Bub1 and other substrates. ATXN7L3B shares 74% identity with the N-terminal region of ATXN7L3, but the functions of ATXN7L3B are not known. Here we report that ATXN7L3B interacts with ENY2, but not other SAGA components. Even though ATXN7L3B localizes in the cytoplasm, ATXN7L3B overexpression increases H2Bub1 levels, while overexpression of ATXN7L3 decreases H2Bub1 levels...
September 6, 2016: Molecular and Cellular Biology
Gloria Lopez-Castejon, Mariola J Edelmann
Inflammation is a protective response of the organism to tissue injury or infection. It occurs when the immune system recognizes Pathogen-Associated Molecular Patterns (PAMPs) or Damage-Associated Molecular Pattern (DAMPs) through the activation of Pattern Recognition Receptors. This initiates a variety of signalling events that conclude in the upregulation of proinflammatory molecules, which initiate an appropriate immune response. This response is tightly regulated since any aberrant activation of immune responses would have severe pathological consequences such as sepsis or chronic inflammatory and autoimmune diseases...
2016: Mediators of Inflammation
J Izrailit, A Jaiswal, W Zheng, M F Moran, M Reedijk
Expression of the Notch ligand JAG1 and Notch pathway activation promote poor prognosis, basal-like breast cancer. We have recently shown that the pseudokinase Tribbles homolog 3 (TRB3) regulates JAG1 expression in this malignancy. TRB3 is a stress and metabolic sensor, and here we show that nutrient deprivation or endoplasmic reticulum stress markedly upregulate TRB3, which serves as a scaffold for the deubiquitinase USP9x. USP9x in turn stimulates JAG1 activity through two mechanisms: (1) through TRB3 deubiquitination and stabilization, and (2) through deubiquitination and activation of Mind Bomb 1, an E3 ligase required for JAG1 ubiquitination-mediated endocytosis and Notch activation...
September 5, 2016: Oncogene
Paul R Elliott, Derek Leske, Matous Hrdinka, Katrin Bagola, Berthe K Fiil, Stephen H McLaughlin, Jane Wagstaff, Norbert Volkmar, John C Christianson, Benedikt M Kessler, Stefan M V Freund, David Komander, Mads Gyrd-Hansen
The linear ubiquitin chain assembly complex (LUBAC) regulates immune signaling, and its function is regulated by the deubiquitinases OTULIN and CYLD, which associate with the catalytic subunit HOIP. However, the mechanism through which CYLD interacts with HOIP is unclear. We here show that CYLD interacts with HOIP via spermatogenesis-associated protein 2 (SPATA2). SPATA2 interacts with CYLD through its non-canonical PUB domain, which binds the catalytic CYLD USP domain in a CYLD B-box-dependent manner. Significantly, SPATA2 binding activates CYLD-mediated hydrolysis of ubiquitin chains...
September 15, 2016: Molecular Cell
Chao Zhang, Jing Lu, Quan-Wu Zhang, Wei Zhao, Jia-Hui Guo, Shan-Ling Liu, Ying-Li Wu, Bin Jiang, Feng-Hou Gao
The Ki-67 antigen (Ki-67) is the most reliable immunohistochemical marker for evaluation of cell proliferation in non-small cell lung cancer. However, the mechanisms underlying the regulation of protein levels of Ki-67 in non-small cell lung cancer have remained elusive. In this study, we found that Ki-67 and ubiquitin-specific processing protease 7 (USP7) protein were highly expressed in the nucleus of non-small cell lung cancer cells. Furthermore, statistical analysis uncovered the existence of a strong correlation between Ki-67 and USP7 levels...
October 2016: International Journal of Biochemistry & Cell Biology
Xiao-Xia Jiang, Yu Liu, Hong Li, Yaping Gao, Rong Mu, Jianping Guo, Jing Zhang, Yan-Mei Yang, Fengjun Xiao, Bing Liu, Changyong Wang, Beifen Shen, Si-Yi Chen, Zhanguo Li, Guang Yang
The aberrant expansion of B1a cells has been observed in several murine autoimmune disease models; however, the mechanism of such proliferation of B1a cells is still limited. Here, we identify that Myb Like, SWIRM And MPN Domains 1 (MYSM1), a histone H2A deubiquitinase, plays an intrinsic role in the proliferation of B1a cells where MYSM1 deficiency results in the increased proliferation of B1a cells in mice. We demonstrate that MYSM1 recruits c-Myc to the promoter of miR-150 and stimulates the transcription of miR-150...
August 31, 2016: Oncotarget
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"