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histone ubiquitination

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https://www.readbyqxmd.com/read/28737508/targeting-nek2-attenuates-glioblastoma-growth-and-radioresistance-by-destabilizing-histone-methyltransferase-ezh2
#1
Jia Wang, Peng Cheng, Marat S Pavlyukov, Hai Yu, Zhuo Zhang, Sung-Hak Kim, Mutsuko Minata, Ahmed Mohyeldin, Wanfu Xie, Dongquan Chen, Violaine Goidts, Brendan Frett, Wenhao Hu, Hongyu Li, Yong Jae Shin, Yeri Lee, Do-Hyun Nam, Harley I Kornblum, Maode Wang, Ichiro Nakano
Accumulating evidence suggests that glioma stem cells (GSCs) are important therapeutic targets in glioblastoma (GBM). In this study, we identified NIMA-related kinase 2 (NEK2) as a functional binding protein of enhancer of zeste homolog 2 (EZH2) that plays a critical role in the posttranslational regulation of EZH2 protein in GSCs. NEK2 was among the most differentially expressed kinase-encoding genes in GSC-containing cultures (glioma spheres), and it was required for in vitro clonogenicity, in vivo tumor propagation, and radioresistance...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28734548/ubiquitin-like-modifications-in-the-dna-damage-response
#2
REVIEW
Zhifeng Wang, Wei-Guo Zhu, Xingzhi Xu
Genomic DNA is damaged at an extremely high frequency by both endogenous and environmental factors. An improper response to DNA damage can lead to genome instability, accelerate the aging process and ultimately cause various human diseases, including cancers and neurodegenerative disorders. The mechanisms that underlie the cellular DNA damage response (DDR) are complex and are regulated at many levels, including at the level of post-translational modification (PTM). Since the discovery of ubiquitin in 1975 and ubiquitylation as a form of PTM in the early 1980s, a number of ubiquitin-like modifiers (UBLs) have been identified, including small ubiquitin-like modifiers (SUMOs), neural precursor cell expressed, developmentally down-regulated 8 (NEDD8), interferon-stimulated gene 15 (ISG15), human leukocyte antigen (HLA)-F adjacent transcript 10 (FAT10), ubiquitin-fold modifier 1 (UFRM1), URM1 ubiquitin-related modifier-1 (URM1), autophagy-related protein 12 (ATG12), autophagy-related protein 8 (ATG8), fan ubiquitin-like protein 1 (FUB1) and histone mono-ubiquitylation 1 (HUB1)...
July 11, 2017: Mutation Research
https://www.readbyqxmd.com/read/28723619/a-novel-sharpin-prmt5-h3r2me1-axis-is-essential-for-lung-cancer-cell-invasion
#3
Tingxiong Fu, Xiuwei Lv, Qingzhi Kong, Changjing Yuan
SHARPIN (Shank-associated RH domain interacting protein) is the main component of the linear ubiquitin chain activation complex (LUBAC). SHARPIN is involved in regulating inflammation and cancer progression. However, whether SHARPIN plays an important role in lung cancer metastasis and the potential underlying mechanism are still unknown. Here, for the first time, we reported that SHARPIN expression is closely related to lung cancer progression. Moreover, SHARPIN plays a central role in controlling lung cancer cell metastasis...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28712876/drosophila-sce-dring-e3-ligase-inhibits-apoptosis-in-a-dp53-dependent-manner
#4
Rocío Simón, Carolina J Simoes da Silva, Sol Fereres, Ana Busturia
The Polycomb group (PcG) of proteins control developmental gene silencing and are highly conserved between flies and mammals. PcG proteins function by controlling post-translational modification of histones, such as ubiquitylation, which impacts chromatin compaction and thus gene transcription. Changes in PcG cellular levels have drastic effects on organismal development and are involved in the generation of human pathologies such as cancer. However, the mechanisms controlling their levels of expression and their physiological effects are only partially understood...
July 13, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28690313/the-hdac-inhibitor-panobinostat-lbh589-exerts-in-vivo-anti-leukaemic-activity-against-mll-rearranged-acute-lymphoblastic-leukaemia-and-involves-the-rnf20-rnf40-wac-h2b-ubiquitination-axis
#5
P G Castro, E H J van Roon, S S M Pinhanços, L Trentin, P Schneider, M Kerstjens, G Te Kronnie, O Heidenreich, R Pieters, R W Stam
MLL-rearranged acute lymphoblastic leukaemia (ALL) represents an aggressive malignancy in infants (<1 year of age), associated with poor outcome. Current treatment intensification is not further possible, and novel therapy strategies are needed. Notably, MLL-rearranged ALL is characterised by a strongly deregulated epigenome and shows sensitivity to epigenetic perturbators. Here, we demonstrate the in vivo efficacy of the histone deacetylase inhibitor Panobinostat (LHB589) using xenograft mouse models of MLL-rearranged ALL...
July 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28687618/huwe1-sustains-normal-ovarian-epithelial-cell-transformation-and-tumor-growth-through-the-histone-h1-3-h19-cascade
#6
Dong Yang, Bin Sun, Xiaohong Zhang, Daomei Cheng, Xiaoping Yu, Lanzhen Yan, Lei Li, Sanqi An, Hua Jiang, Anna Lasorella, Antonio Iavarone, Shu Zhang, Fangdong Zou, Xudong Zhao
Ubiquitination-directed protein degradation is important in many cancers for tumor initiation and maintenance, and E3 ligases containing HECT domains are emerging as new therapeutic targets. In contrast to many other E3 ligases, the role of HUWE1 in ovarian cancer where HUWE1 is dysregulated has been unclear. Here we report that genetic deletion of Huwe1 in the mouse inhibits transformation of ovary surface epithelium cells without significantly affecting cell survival and apoptosis, and that Huwe1 deletion after tumors have been initiated inhibits tumor growth...
July 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28677248/identification-of-suitable-reference-genes-during-the-formation-of-chlamydospores-in-clonostachys-rosea-67-1
#7
Jun Zhang, Zhanbin Sun, Shidong Li, Manhong Sun
Clonostachys rosea is a potential biocontrol fungus that can produce highly resistant chlamydospores under specific conditions. To investigate the genes related to chlamydospore formation, we identified reliable reference genes for quantification of gene expression in C. rosea 67-1 during sporulation. In this study, nine reference genes, actin (ACT), elongation factor 1 (EF1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), histone (HIS), RNA polymerase II CTD phosphatase Fcp1 (RPP), succinate-semialdehyde dehydrogenase (SSD), TATA-binding protein (TBP), ubiquitin (UBQ), and ubiquitin-conjugating enzyme (UCE), were selected and cloned from 67-1, and their expression stability during chlamydospore formation was determined using reverse transcription quantitative PCR and assessed using the software geNorm, NormFinder and BestKeeper...
July 5, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28668087/inhibition-of-hdac6-activity-through-interaction-with-ranbpm-and-its-associated-ctlh-complex
#8
Louisa M Salemi, Matthew E R Maitland, Eyal R Yefet, Caroline Schild-Poulter
BACKGROUND: Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase that promotes many cellular processes that lead to cell transformation and tumour development. We previously documented an interaction between Ran-Binding Protein M (RanBPM) and HDAC6 and found that RanBPM expression inhibits HDAC6 activity. RanBPM is part of a putative E3 ubiquitin ligase complex, termed the C-terminal to LisH (CTLH) complex. Here, we investigated the involvement of the CTLH complex on HDAC6 inhibition and assessed the outcome of this regulation on the cellular motility induced by HDAC6...
July 1, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28663576/setd2-and-histone-h3-lysine-36-methylation-deficiency-in-advanced-systemic-mastocytosis
#9
G Martinelli, M Mancini, C De Benedittis, M Rondoni, C Papayannidis, M Manfrini, M Meggendorfer, R Calogero, V Guadagnuolo, M C Fontana, L Bavaro, A Padella, E Zago, L Pagano, R Zanotti, L Scaffidi, G Specchia, F Albano, S Merante, C Elena, P Savini, D Gangemi, P Tosi, F Ciceri, G Poletti, L Riccioni, F Morigi, M Delledonne, T Haferlach, M Cavo, P Valent, S Soverini
The molecular basis of advanced systemic mastocytosis (SM) is not fully understood and despite novel therapies the prognosis remains dismal. Exome sequencing of an index-patient with mast cell leukemia (MCL) uncovered biallelic loss-of-function mutations in the SETD2 histone methyltransferase gene. Copy-neutral loss-of-heterozygosity at 3p21.3 (where SETD2 maps) was subsequently found in SM patients and prompted us to undertake an in-depth analysis of SETD2 copy number, mutation status, transcript expression and methylation levels, as well as functional studies in the HMC-1 cell line and in a validation cohort of 57 additional cases with SM, including MCL, aggressive SM and indolent SM...
June 16, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28663238/remarkable-evolutionary-conservation-of-anti-obesity-adipose-wdtc1-homologs-in-animals-and-plants
#10
Eric Ducos, Valentin Vergès, Thomas Dugé de Bernonville, Nathalie Blanc, Nathalie Giglioli-Guivarc'h, Christelle Dutilleul
ASG2 (Altered Seed Germination 2) is a prenylated protein in Arabidopsis thaliana that participates to abscisic acid signaling and is proposed to act as a substrate adaptor for the DDB1-CUL4 E3 ubiquitin ligase complex. ASG2 harbors WD40 and TetratricoPeptide Repeat (TPR) domains, and resembles the well-conserved animal gene called ADP (anti-obesity factor ADIPOSE) in fly and WDTC1 (WD40 and TPR 1) in humans. Loss of function of WDTC1 results in an increase in adipocytes, fat accumulation and obesity. Anti-adipogenic functions of WDTC1 involve regulation of fat-related gene transcription, notably through its binding to histone deacetylases...
June 29, 2017: Genetics
https://www.readbyqxmd.com/read/28655885/mir-15a-mir-16-down-regulates-bmi1-impacting-ub-h2a-mediated-dna-repair-and-breast-cancer-cell-sensitivity-to-doxorubicin
#11
Nibedita Patel, Koteswara Rao Garikapati, Raj K Pandita, Dharmender Kumar Singh, Tej K Pandita, Utpal Bhadra, Manika Pal Bhadra
The B-lymphoma Moloney murine leukemia virus insertion region-1 protein (BMI1) acts as an oncogene in various cancers, including breast cancer. Recent evidence suggests that BMI1 is rapidly recruited to sites of DNA double strand breaks where it facilitates histone H2A ubiquitination and DNA double strand break repair by homologous recombination. Here we show that miR-15a and miR-16 expression is decreased during the initial period after DNA damage where it would otherwise down-regulate BMI1, impairing DNA repair...
June 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28655758/ubiquitin-specific-peptidase-7-usp7-mediated-deubiquitination-of-the-histone-deacetylase-sirt7-regulates-gluconeogenesis
#12
Lu Jiang, Jiannan Xiong, Junsi Zhan, Fengjie Yuan, Ming Tang, Chaohua Zhang, Ziyang Cao, Yongcan Chen, Xiaopeng Lu, Yinglu Li, Hui Wang, Lina Wang, Jiadong Wang, Wei-Guo Zhu, Haiying Wang
Sirtuin 7 (SIRT7), a member of the NAD+-dependent class III histone deacetylases (HDACs), is involved in the regulation of various cellular processes and in resisting various stresses, such as hypoxia, low glucose levels and DNA damage. Interestingly, SIRT7 is linked to the control of glycolysis, suggesting a role in glucose metabolism. Given the important roles of SIRT7, it is critical to clarify how SIRT7 activity is potentially regulated. It has been reported that some transcriptional and post-transcriptional regulatory mechanisms are involved...
June 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28651835/andrographolide-reduced-vegfa-expression-in-hepatoma-cancer-cells-by-inactivating-hif-1%C3%AE-the-involvement-of-jnk-and-mta1-hdca
#13
Liang Shi, Guoqing Zhang, Zhiyong Zheng, Bin Lu, Lili Ji
Andrographolide (Andro) is the main active compound in medicinal herb Andrographis paniculata Nees (Acanthaceae). Vascular endothelial growth factor A (VEGFA), a key pro-angiogenic factor, contributes greatly to tumor growth. The purpose of this study is to observe the inhibition of Andro on VEGFA expression in hepatoma cancer cells and its engaged mechanism. Andro decreased mRNA and protein expression of VEGFA in hepatoma Hep3B and HepG2 cells. Andro also decreased hypoxia-inducible factor 1-alpha (HIF-1α) protein expression and its subsequent nuclear translocation...
June 23, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28650265/autophagy-regulates-dna-repair-through-sqstm1-p62
#14
Yuchen Feng, Daniel J Klionsky
Macroautophagy/autophagy is primarily a degradative pathway that clears malfunctioning cellular components in response to various types of stress. Recent studies have indicated that autophagy also plays an important role in maintaining genome stability. Loss of autophagy is associated with increased damage to DNA, inappropriate amplification of genomic regions and abnormal chromosome number. In a recent paper by Wang et al. the authors uncover a mechanism through which autophagy regulates the ubiquitination of chromatin...
June 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28648780/the-histone-acetyltransferase-mst2-protects-active-chromatin-from-epigenetic-silencing-by-acetylating-the-ubiquitin-ligase-brl1
#15
Valentin Flury, Paula Raluca Georgescu, Vytautas Iesmantavicius, Yukiko Shimada, Tahsin Kuzdere, Sigurd Braun, Marc Bühler
Faithful propagation of functionally distinct chromatin states is crucial for maintaining cellular identity, and its breakdown can lead to diseases such as cancer. Whereas mechanisms that sustain repressed states have been intensely studied, regulatory circuits that protect active chromatin from inactivating signals are not well understood. Here we report a positive feedback loop that preserves the transcription-competent state of RNA polymerase II-transcribed genes. We found that Pdp3 recruits the histone acetyltransferase Mst2 to H3K36me3-marked chromatin...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28630323/role-of-the-cbp-catalytic-core-in-intramolecular-sumoylation-and-control-of-histone-h3-acetylation
#16
Sangho Park, Robyn L Stanfield, Maria A Martinez-Yamout, H Jane Dyson, Ian A Wilson, Peter E Wright
The histone acetyl transferases CREB-binding protein (CBP) and its paralog p300 play a critical role in numerous cellular processes. Dysregulation of their catalytic activity is associated with several human diseases. Previous work has elucidated the regulatory mechanisms of p300 acetyltransferase activity, but it is not known whether CBP activity is controlled similarly. Here, we present the crystal structure of the CBP catalytic core encompassing the bromodomain (BRD), CH2 (comprising PHD and RING), HAT, and ZZ domains at 2...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28624371/histone-ubiquitination-in-the-dna-damage-response
#17
REVIEW
Michael Uckelmann, Titia K Sixma
DNA double strand breaks need to be repaired in an organized fashion to preserve genomic integrity. In the organization of faithful repair, histone ubiquitination plays a crucial role. Recent findings suggest an integrated model for DNA repair regulation through site-specific histone ubiquitination and crosstalk to other posttranslational modifications. Here we discuss how site-specific histone ubiquitination is achieved on a molecular level and how different multi-protein complexes work together to integrate different histone ubiquitination states...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28615292/rtt101-mms1-mms22-coordinates-replication-coupled-sister-chromatid-cohesion-and-nucleosome-assembly
#18
Jingjing Zhang, Di Shi, Xiaoli Li, Lin Ding, Jun Tang, Cong Liu, Katsuhiko Shirahige, Qinhong Cao, Huiqiang Lou
Two sister chromatids must be held together by a cohesion process from their synthesis during S phase to segregation in anaphase. Despite its pivotal role in accurate chromosome segregation, how cohesion is established remains elusive. Here, we demonstrate that yeast Rtt101-Mms1, Cul4 family E3 ubiquitin ligases are stronger dosage suppressors of loss-of-function eco1 mutants than PCNA The essential cohesion reaction, Eco1-catalyzed Smc3 acetylation is reduced in the absence of Rtt101-Mms1. One of the adaptor subunits, Mms22, associates directly with Eco1...
June 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28611184/regulation-of-the-ubiquitylation-and-deubiquitylation-of-creb-binding-protein-modulates-histone-acetylation-and-lung-inflammation
#19
Jianxin Wei, Su Dong, Rachel K Bowser, Andrew Khoo, Lina Zhang, Anastasia M Jacko, Yutong Zhao, Jing Zhao
Cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB)-binding protein (CBP) is a histone acetyltransferase that plays a pivotal role in the control of histone modification and the expression of cytokine-encoding genes in inflammatory diseases, including sepsis and lung injury. We found that the E3 ubiquitin ligase subunit FBXL19 targeted CBP for site-specific ubiquitylation and proteasomal degradation. The ubiquitylation-dependent degradation of CBP reduced the extent of lipopolysaccharide (LPS)-dependent histone acetylation and cytokine release in mouse lung epithelial cells and in a mouse model of sepsis...
June 13, 2017: Science Signaling
https://www.readbyqxmd.com/read/28604711/the-anaphase-promoting-complex-impacts-repair-choice-by-protecting-ubiquitin-signalling-at-dna-damage-sites
#20
Kyungsoo Ha, Chengxian Ma, Han Lin, Lichun Tang, Zhusheng Lian, Fang Zhao, Ju-Mei Li, Bei Zhen, Huadong Pei, Suxia Han, Marcos Malumbres, Jianping Jin, Huan Chen, Yongxiang Zhao, Qing Zhu, Pumin Zhang
Double-strand breaks (DSBs) are repaired through two major pathways, homology-directed recombination (HDR) and non-homologous end joining (NHEJ). While HDR can only occur in S/G2, NHEJ can happen in all cell cycle phases (except mitosis). How then is the repair choice made in S/G2 cells? Here we provide evidence demonstrating that APC(Cdh1) plays a critical role in choosing the repair pathways in S/G2 cells. Our results suggest that the default for all DSBs is to recruit 53BP1 and RIF1. BRCA1 is blocked from being recruited to broken ends because its recruitment signal, K63-linked poly-ubiquitin chains on histones, is actively destroyed by the deubiquitinating enzyme USP1...
June 12, 2017: Nature Communications
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