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SUMOylation

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https://www.readbyqxmd.com/read/28528440/the-human-cmv-ie1-protein-an-offender-of-pml-nuclear-bodies
#1
Myriam Scherer, Eva-Maria Schilling, Thomas Stamminger
PML nuclear bodies (PML-NBs) are SUMOylation-dependent, highly complex protein assemblies that accumulate in the interchromosomal territories of the cell nucleus. Research of the last two decades revealed that many viruses have evolved effector proteins that modify PML-NBs. This correlates with antagonization of individual PML-NB components which act as host cell restriction factors. The multifunctional immediate-early protein IE1 of human cytomegalovirus directly interacts with the PML protein resulting in a disruption of the dot-like structure of PML-NBs...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28527786/sumo-in-the-dna-double-stranded-break-response-similarities-differences-and-co-operation-with-ubiquitin
#2
REVIEW
Joanna R Morris, Alexander J Garvin
In recent years our knowledge of the varied role that ubiquitination plays in promoting signal amplification, novel protein interactions and protein turn-over has progressed rapidly. This is particularly remarkable in the examination of how DNA Double-Strand Breaks (DSBs) are repaired, with many components of the ubiquitin conjugation, de-conjugation and recognition machinery now identified as key factors in DSB repair. In addition, a member of the ubiquitin-like family, SUMO (Small Ubiquitin-like Modifier) has also been recognised as integral for efficient repair...
May 17, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28525371/arsenic-trioxide-and-angiotensin-ii-have-inhibitory-effects-on-herg-protein-expression-evidence-for-the-role-of-pml-sumoylation
#3
Yu Liu, Duo Li, Dan Nie, Shang-Kun Liu, Fang Qiu, Mei-Tong Liu, Yuan-Yuan Li, Jia-Xin Wang, Yan-Xin Liu, Chang-Jiang Dong, Di Wu, Wei Tian, Jia Yang, Wei Mu, Jia-Tong Li, Dan Zhao, Xiao-Feng Wang, Wen-Feng Chu, Bao-Feng Yang
The human ether-a-go-go-related gene (HERG) channel is a novel target for the treatment of drug-induced long QT syndrome, which causes lethal cardiotoxicity. This study is designed to explore the possible role of PML SUMOylation and its associated nuclear bodies (NBs) in the regulation of HERG protein expression. Both arsenic trioxide (ATO) and angiotensin II (Ang II) were able to significantly reduce HERG protein expression, while also increasing PML SUMOylation and accelerating the formation of PML-NBs. Pre-exposure of cardiomyocytes to a SUMOylation chemical inhibitor, ginkgolic acid, or the silencing of UBC9 suppressed PML SUMOylation, subsequently preventing the downregulation of HERG induced by ATO or Ang II...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28520516/mesenchymal-stem-cell-migration-and-proliferation-are-mediated-by-hypoxia-inducible-factor-1%C3%AE-upstream-of-notch-and-sumo-pathways
#4
María Ciria, Nahuel A García, Imelda Ontoria-Oviedo, Hernán González-King, Rubén Carrero, José Luis De La Pompa, José Anastasio Montero, Pilar Sepúlveda
Mesenchymal stem cells (MSCs) are effective in treating several pathologies. We and others have demonstrated that hypoxia or hypoxia-inducible factor 1 alpha (HIF-1α) stabilization improves several MSC functions, including cell adhesion, migration, and proliferation, thereby increasing their therapeutic potential. To further explore the mechanisms induced by HIF-1α in MSCs, we studied its relationship with Notch signaling and observed that overexpression of HIF-1α in MSCs increased protein levels of the Notch ligands Jagged 1-2 and Delta-like (Dll)1, Dll3, and Dll4 and potentiated Notch signaling only when this pathway was activated...
May 18, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28512234/a-guide-for-targeted-sumo-removal
#5
REVIEW
Nalini Dhingra, Xiaolan Zhao
SUMO homeostasis is important for many cellular processes. In the current issue of Genes & Development, Liang and colleagues (pp. 802-815) demonstrate how a desumoylation enzyme is targeted to the nucleolus for removing SUMO from specific substrates and how curtailing sumoylation levels can regulate transcription in this nuclear compartment.
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28495965/pias3-is-necessary-for-dorso-ventral-patterning-and-visual-response-of-retinal-cones-but-is-not-required-for-rod-photoreceptor-differentiation
#6
Christie K Campla, Hannah Breit, Lijin Dong, Jessica D Gumerson, Jerome E Roger, Anand Swaroop
Protein inhibitor of activated Stat 3 (Pias3) is implicated in guiding specification of rod and cone photoreceptors through posttranslational modification of key retinal transcription factors. To investigate its role during retinal development, we deleted exon 2-5 of the mouse Pias3 gene, which resulted in complete loss of the Pias3 protein. Pias3(-/-) mice did not show any overt phenotype, and retinal lamination appeared normal even at 18 months. We detected reduced photopic b-wave amplitude by electroretinography following green light stimulation of postnatal day (P) 21 Pias3(-/-) retina, suggesting a compromised visual response of medium wavelength (M) cones...
May 11, 2017: Biology Open
https://www.readbyqxmd.com/read/28493978/identification-of-the-sumo-e3-ligase-pias1-as-a-potential-survival-biomarker-in-breast-cancer
#7
Ayan Chanda, Angela Chan, Lili Deng, Elizabeth N Kornaga, Emeka K Enwere, Donald G Morris, Shirin Bonni
Metastasis is the ultimate cause of breast cancer related mortality. Epithelial-mesenchymal transition (EMT) is thought to play a crucial role in the metastatic potential of breast cancer. Growing evidence has implicated the SUMO E3 ligase PIAS1 in the regulation of EMT in mammary epithelial cells and breast cancer metastasis. However, the relevance of PIAS1 in human cancer and mechanisms by which PIAS1 might regulate breast cancer metastasis remain to be elucidated. Using tissue-microarray analysis (TMA), we report that the protein abundance and subcellular localization of PIAS1 correlate with disease specific overall survival of a cohort of breast cancer patients...
2017: PloS One
https://www.readbyqxmd.com/read/28486108/trib3-promotes-apl-progression-through-stabilization-of-the-oncoprotein-pml-rar%C3%AE-and-inhibition-of-p53-mediated-senescence
#8
Ke Li, Feng Wang, Wen-Bin Cao, Xiao-Xi Lv, Fang Hua, Bing Cui, Jiao-Jiao Yu, Xiao-Wei Zhang, Shuang Shang, Shan-Shan Liu, Jin-Mei Yu, Ming-Zhe Han, Bo Huang, Ting-Ting Zhang, Xia Li, Jian-Dong Jiang, Zhuo-Wei Hu
Acute promyelocytic leukemia (APL) is driven by the oncoprotein PML-RARα, which antagonizes myeloid differentiation and promotes APL-initiating cell self-renewal. Combined all-trans retinoic acid (ATRA) with arsenic trioxide (As2O3) or chemotherapy dramatically improves the prognosis of APL patients. Here we report that expression of pseudokinase Tribble 3 (TRIB3) associates positively with APL progression and therapeutic resistance. The elevated TRIB3 expression promotes APL by interacting with PML-RARα and suppressing its sumoylation, ubiquitylation, and degradation...
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28481731/posttranslational-modifications-in-spermatozoa-and-effects-on-male-fertility-and-sperm-viability
#9
Rahim Dad Brohi, Li-Jun Huo
Spermatogenesis is a complex and highly regulated process. The ability of spermatozoa to perform its function depends on multiple physiological and genetic factors that are not fully understood. Notably, due to lack of transcriptional and translational activity in spermatozoa, posttranslational modifications (PTMs) play key roles in determining their viability. PTMs not only confer structural changes in the proteome of the spermatozoa cells, but also increase the diversity of the proteome and introduce specific modifications that could be translated into functional changes in the affected spermatozoa...
May 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28475868/glucocorticoid-receptor-megatrans-switching-mediates-the-repression-of-an-er%C3%AE-regulated-transcriptional-program
#10
Feng Yang, Qi Ma, Zhijie Liu, Wenbo Li, Yuliang Tan, Chunyu Jin, Wubin Ma, Yiren Hu, Jia Shen, Kenneth A Ohgi, Francesca Telese, Wen Liu, Michael G Rosenfeld
The molecular mechanisms underlying the opposing functions of glucocorticoid receptors (GRs) and estrogen receptor α (ERα) in breast cancer development remain poorly understood. Here we report that, in breast cancer cells, liganded GR represses a large ERα-activated transcriptional program by binding, in trans, to ERα-occupied enhancers. This abolishes effective activation of these enhancers and their cognate target genes, and it leads to the inhibition of ERα-dependent binding of components of the MegaTrans complex...
May 4, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28475613/sumo-targeted-ubiquitin-ligase-activity-can-either-suppress-or-promote-genome-instability-depending-on-the-nature-of-the-dna-lesion
#11
Minghua Nie, Bettina A Moser, Toru M Nakamura, Michael N Boddy
The posttranslational modifiers SUMO and ubiquitin critically regulate the DNA damage response (DDR). Important crosstalk between these modifiers at DNA lesions is mediated by the SUMO-targeted ubiquitin ligase (STUbL), which ubiquitinates SUMO chains to generate SUMO-ubiquitin hybrids. These SUMO-ubiquitin hybrids attract DDR proteins able to bind both modifiers, and/or are degraded at the proteasome. Despite these insights, specific roles for SUMO chains and STUbL in the DDR remain poorly defined. Notably, fission yeast defective in SUMO chain formation exhibit near wild-type resistance to genotoxins and moreover, have a greatly reduced dependency on STUbL activity for DNA repair...
May 5, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28474569/the-involvement-of-post-translational-modifications-in-alzheimer-s-disease
#12
S Marcelli, Massimo Corbo, Filomena Iannuzzi, Lucia Negri, Fabio Blandini, Robert Nisticò, M Feligioni
Alzheimer’s disease (AD) is a neurodegenerative disorder recognized as the most common cause of chronic dementia among the ageing population. AD is histopathologically characterized by progressive loss of neurons and deposits of insoluble proteins, primarily composed of amyloid-β pelaques and neurofibrillary tangles (NFTs). Several molecular processes contribute to the formation of AD cellular hallmarks. Among them, post-translational modifications (PTMs) represent an attractive mechanism underlying the formation of covalent bonds between chemical groups/peptides to target proteins, which ultimately result modified in their function...
May 4, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28465351/an-hnf4%C3%AE-microrna-194-192-signaling-axis-maintains-hepatic-cell-function
#13
Aoi Morimoto, Mana Kannari, Yuichi Tsuchida, Shota Sasaki, Chinatsu Saito, Tsuyoshi Matsuta, Tsukasa Maeda, Megumi Akiyama, Takahiro Nakamura, Masakiyo Sakaguchi, Nobukazu Nameki, Frank J Gonzalez, Yusuke Inoue
HNF4α controls the expression of liver-specific protein-coding genes. However, some microRNAs (miRNAs) are also modulated by HNF4α, and it is not known whether they are direct targets of HNF4α, and whether they influence the hepatic function. In this study, we found that HNF4α regulates miRNAs, indicated by marked down-regulation of miR-194 and miR-192 (miR-194/192) in liver-specific Hnf4a-null (Hnf4a(ΔH)) mice. Transactivation of the shared miR-194/192 promoter was dependent on HNF4α expression, indicating that miR194/192 is a target gene of HNF4α...
May 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28458782/protein-post-translational-modifications-in-silico-prediction-tools-and-molecular-modeling
#14
REVIEW
Martina Audagnotto, Matteo Dal Peraro
Post-translational modifications (PTMs) occur in almost all proteins and play an important role in numerous biological processes by significantly affecting proteins' structure and dynamics. Several computational approaches have been developed to study PTMs (e.g., phosphorylation, sumoylation or palmitoylation) showing the importance of these techniques in predicting modified sites that can be further investigated with experimental approaches. In this review, we summarize some of the available online platforms and their contribution in the study of PTMs...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28455449/identification-of-a-new-sumo-interacting-motif-in-piasy
#15
Kawaljit Kaur, Hyewon Park, Nootan Pandey, Yoshiaki Azuma, Roberto N De Guzman
SUMO conjugation is a reversible post-translational modification process implicated in the regulation of gene transcription, DNA repair, and cell cycle. SUMOylation depends on the sequential activities of E1 activating, E2 conjugating, and E3 ligating enzymes. SUMO E3 ligases enhance transfer of SUMO from the charged E2 enzyme to the substrate. We have previously identified PIASy, a member of the Siz/PIAS RING family of SUMO E3 ligases, as essential for mitotic chromosomal SUMOylation in frog egg extracts and demonstrated that it can mediate effective SUMOylation...
April 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28451587/the-interplay-of-cofactor-interactions-and-post-translational-modifications-in-the-regulation-of-the-aaa-atpase-p97
#16
REVIEW
Petra Hänzelmann, Hermann Schindelin
The hexameric type II AAA ATPase (ATPase associated with various activities) p97 (also referred to as VCP, Cdc48, and Ter94) is critically involved in a variety of cellular activities including pathways such as DNA replication and repair which both involve chromatin remodeling, and is a key player in various protein quality control pathways mediated by the ubiquitin proteasome system as well as autophagy. Correspondingly, p97 has been linked to various pathophysiological states including cancer, neurodegeneration, and premature aging...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28446721/senp3-grants-tight-junction-integrity-and-cytoskeleton-architecture-in-mouse-sertoli-cells
#17
Di Wu, Chun-Jie Huang, Faheem Ahmed Khan, Xiao-Fei Jiao, Xiao-Ming Liu, Nuruliarizki Shinta Pandupuspitasari, Rahim Dad Brohi, Li-Jun Huo
Germ cells develop in a sophisticated immune privileged microenvironment provided by specialized junctions contiguous the basement membrane of the adjacent Sertoli cells that constituted the blood-testis barrier (BTB) in seminiferous epithelium of testis in mammals. Deciphering the molecular regulatory machinery of BTB activity is central to improve male fertility and the role of post-translational modification including SUMOylation pathway is one of the key factors. Herein, we unveiled the mystery of the SUMO-2/3 specific protease SENP3 (Sentrin-specific protease 3) in BTB dynamics regulation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28440894/chromatin-sumoylation-in-heat-stress-to-protect-pause-and-organise-sumo-stress-response-on-chromatin
#18
REVIEW
Einari A Niskanen, Jorma J Palvimo
Post-translational modifications, e.g. SUMO modifications (SUMOylation), provide a mechanism for swiftly changing a protein's activity. Various stress conditions trigger a SUMO stress response (SSR) - a stress-induced rapid change in the conjugation of SUMO to multiple proteins, which predominantly targets nuclear proteins. The SSR has been postulated to protect stressed cells by preserving the functionality of crucial proteins. However, it is unclear how it exerts its protective functions. Interestingly, heat stress (HS) increases SUMOylation of proteins at active promoters and enhancers...
April 25, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28440563/the-sumo-e3-ligase-mdsiz1-promotes-anthocyanin-accumulation-by-sumoylating-mdmyb1-under-low-temperature-conditions-in-apple
#19
Li-Jie Zhou, Yuan-Yuan Li, Rui-Fen Zhang, Chun-Ling Zhang, Xing-Bin Xie, Cheng Zhao, Yu-Jin Hao
MdMYB1 acts as a crucial component of the MYB-bHLH-WD40 (MBW) complex to regulate anthocyanin biosynthesis in red-skinned apples (Malus domestica), but little is known about its posttranslational regulation. Here, a SUMO E3 ligase MdSIZ1 was screened out as an MdMYB1-interacting protein with a yeast two-hybridization approach. The interaction between MdSIZ1 and MdMYB1 was further verified with pull-down and CoIP assays. Furthermore, it was found that MdSIZ1 directly sumoylated MdMYB1 proteins in vivo and in vitro, especially under moderately low temperature (17 °C) conditions, and that this sumoylation was required for MdMYB1 protein stability...
April 25, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28435066/cross-talk-between-sumoylation-and-phosphorylation-in-mouse-spermatocytes
#20
Yuxuan Xiao, Benjamin Lucas, Elana Molcho, Margarita Vigodner
The meiotic G2/M1 transition is mostly regulated by posttranslational modifications, however, the cross-talk between different posttranslational modifications is not well-understood, especially in spermatocytes. Sumoylation has emerged as a critical regulatory event in several developmental processes, including reproduction. In mouse oocytes, inhibition of sumoylation caused various meiotic defects and led to aneuploidy. However, the role of sumoylation in male reproduction has only begun to be elucidated. Given the important role of several SUMO targets (including kinases) in meiosis, in this study, the role of sumoylation was addressed by monitoring the G2/M1 transition in pachytene spermatocytes in vitro upon inhibition of sumoylation...
April 20, 2017: Biochemical and Biophysical Research Communications
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