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Rita Hleihel, Behzad Khoshnood, Ingrid Dacklin, Hayssam Omran, Carine Mouawad, Zeina Dassouki, Marwan El-Sabban, Margret Shirinian, Caroline Grabbe, Ali Bazarbachi
BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy secondary to chronic human T-cell lymphotropic virus 1 infection, triggered by the virally encoded oncoprotein Tax. The transforming activity and subcellular localization of Tax is strongly influenced by posttranslational modifications, among which ubiquitylation and SUMOylation have been identified as key regulators of the nuclear/cytoplasmic shuttling of Tax, as well as its ability to activate NF-κB signaling...
April 17, 2018: Retrovirology
Caiyun Liu, Zhigang Li, Junjie Xing, Jun Yang, Zhao Wang, Hong Zhang, Deng Chen, You-Liang Peng, Xiao-Lin Chen
Protein post-translational modifications play critical roles in cellular processes, development and stress response. The small ubiquitin-like modifier (SUMO) to proteins is one of the essential modifications in eukaryotes, but its function remains largely unknown in plant pathogenic fungi. We present a comprehensive analysis combined with proteomic, molecular and cellular approaches to explore the roles of sumoylation in the model plant fungal pathogen, Magnaporthe oryzae. We found the SUMO pathway plays key roles in colony growth, conidia formation and virulence to the host, as well as cell-cycle-related phenotypes...
April 16, 2018: New Phytologist
Joo Yong Kim, Bong Soo Park, Sang Woo Park, Han Yong Lee, Jong Tae Song, Hak Soo Seo
Nitrate reductases (NRs) catalyze the first step in the reduction of nitrate to ammonium. NR activity is regulated by sumoylation through the E3 ligase activity of AtSIZ1. However, it is not clear how NRs interact with AtSIZ1 in the cell, or how nitrogen sources affect NR levels and their cellular localization. Here, we show that the subcellular localization of NRs is modulated by the E3 SUMO (Small ubiquitin-related modifier) ligase AtSIZ1 and that NR protein levels are regulated by nitrogen sources. Transient expression analysis of GFP fusion proteins in onion epidermal cells showed that the NRs NIA1 and NIA2 localize to the cytoplasmic membrane, and that AtSIZ1 localizes to the nucleoplasm, including nuclear bodies, when expressed separately, whereas NRs and AtSIZ1 localize to the nucleus when co-expressed...
April 15, 2018: International Journal of Molecular Sciences
Takuma Maruyama, Harmony Wada, Yoichiro Abe, Takako Niikura
SUMOylation, a post-translational modification of lysine residues by small ubiquitin-like modifier (SUMO) proteins, has been implicated in the pathogenesis of neurodegenerative disorders including Alzheimer's disease (AD), and in neuron- and astrocyte-specific physiological functions. Global SUMOylation is increased in the AD mouse brain in the pre-plaque-forming stage but returns to wild-type levels in the plaque-bearing stage. To clarify the reason for the transient change in SUMOylation, we analyzed the alteration of global SUMOylation induced by AD-associated cytotoxic stimuli in neurons and astrocytes individually...
April 13, 2018: Biochemical and Biophysical Research Communications
Christopher T Coey, Alexander C Drohat
Thymine DNA glycosylase (TDG) excises thymine from mutagenic G·T mispairs generated by deamination of 5-methylcytosine (mC) and it removes two mC derivatives, 5-formylcytosine (fC) and 5-carboxylcytosine (caC), in a multistep pathway for DNA demethylation. TDG is modified by small ubiquitin-like modifier (SUMO) proteins, but the impact of sumoylation on TDG activity is poorly defined and the functions of TDG sumoylation remain unclear. We determined the effect of TDG sumoylation, by SUMO-1 or SUMO-2, on substrate binding and catalytic parameters...
April 12, 2018: Nucleic Acids Research
Chunlin Zuo, Lijun Wang, Raghavendra M Kamalesh, Margot E Bowen, Douglas C Moore, Mark S Dooner, Anthony M Reginato, Qian Wu, Christoph Schorl, Yueming Song, Matthew L Warman, Benjamin G Neel, Michael G Ehrlich, Wentian Yang
Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor (OCP), and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OCPs are incompletely understood. We asked whether the ubiquitously expressed protein-tyrosine phosphatase SHP2 (encoded by Ptpn11 ) affects skeletal lineage commitment by conditionally deleting Ptpn11 in mouse limb and head mesenchyme using "Cre-loxP"-mediated gene excision. SHP2-deficient mice have increased cartilage mass and deficient ossification, suggesting that SHP2-deficient OCPs become chondrocytes and not osteoblasts...
2018: Bone Research
Virginia Rider, Nabih I Abdou, Bruce F Kimler, Nanyan Lu, Susan Brown, Brooke L Fridley
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease resulting from abnormal interactions between T and B cells. The acquisition of SLE is linked to genetic susceptibility, and diverse environmental agents can trigger disease onset in genetically susceptible individuals. However, the strongest risk factor for developing SLE is being female (9:1 female to male ratio). The female sex steroid, estradiol, working through its receptors, contributes to the gender bias in SLE although the mechanisms remain enigmatic...
2018: Frontiers in Immunology
Shujun Han, Yibo Ren, Wangxiao He, Huadong Liu, Zhe Zhi, Xinliang Zhu, Tielin Yang, Yu Rong, Bohan Ma, Timothy J Purwin, Zhenlin Ouyang, Caixia Li, Xun Wang, Xueqiang Wang, Huizi Yang, Yan Zheng, Andrew E Aplin, Jiankang Liu, Yongping Shao
In the original version of this Article, financial support was not fully acknowledged. The PDF and HTML versions of the Article have now been corrected to include the following: The National Basic Research Program (2015CB553602 to J.L.), the National Natural Science Foundation of China (31570777, 91649106, 31770917 to J.L.) and Tianjin Applied Basic and Frontier Tech Major Project (12JCZDJC34400 to J.L.) and Tianjin Higher Education Sci-Tech Development Project (20112D05 to J.L.).
April 6, 2018: Nature Communications
Joshua D Bernstock, Daniel G Ye, Yang-Ja Lee, Florian Gessler, Gregory K Friedman, Wei Zheng, John M Hallenbeck
No abstract text is available yet for this article.
March 2018: Neural Regeneration Research
Sibylle Pfammatter, Eric Bonneil, Francis P McManus, Pierre Thibault
The small ubiquitin-like modifier (SUMO) is a member of the family of ubiquitin-like modifiers (UBLs) and is involved in important cellular processes, including DNA damage response, meiosis and cellular trafficking. The large-scale identification of SUMO peptides in a site-specific manner is challenging not only because of the low abundance and dynamic nature of this modification, but also due to the branched structure of the corresponding peptides that further complicate their identification using conventional search engines...
April 5, 2018: Journal of the American Society for Mass Spectrometry
Mariana Fuertes, Melanie Sapochnik, Lucas Tedesco, Sergio Senin, Alejandra Attorresi, Pablo Ajler, Guillermo Carrizo, Andrés Cervio, Gustavo Sevlever, Juan José Bonfiglio, Günter K Stalla, Eduardo Arzt
Increased levels of the proto-oncogene pituitary tumor transforming gene 1 (PTTG) have been repeatedly reported in several human solid tumors, especially in endocrine-related tumors such as pituitary adenomas. Securin PTTG has a critical role in pituitary tumorigenesis. However, the cause of upregulation has not been found yet, despite analyses made at the gene, promoter and mRNA level that show that no mutations, epigenetic modifications or other mechanisms that deregulate its expression may explain its overexpression and action as an oncogene...
April 5, 2018: Endocrine-related Cancer
Mona Abed, Eliya Bitman-Lotan, Amir Orian
The ubiquitin and SUMO (small ubiquitin-like modifier) pathways modify proteins that in turn regulate diverse cellular processes, embryonic development, and adult tissue physiology. These pathways were originally discovered biochemically in vitro, leading to a long-standing challenge of elucidating both the molecular cross-talk between these pathways and their biological importance. Recent discoveries in Drosophila established that ubiquitin and SUMO pathways are interconnected via evolutionally conserved SUMO-targeted ubiquitin ligase (STUbL) proteins...
January 1, 2018: Journal of Developmental Biology
Pengran Wang, Shirine Benhenda, Haiyan Wu, Valérie Lallemand-Breitenbach, Tao Zhen, Florence Jollivet, Laurent Peres, Yuwen Li, Sai-Juan Chen, Zhu Chen, Hugues de Thé, Guoyu Meng
ProMyelocyticLeukemia nuclear bodies (PML NBs) are stress-regulated domains directly implicated in acute promyelocytic leukemia eradication. Most TRIM family members bind ubiquitin E2s and many acquire ligase activity upon RING dimerization. In contrast, PML binds UBC9, the SUMO E2 enzyme. Here, using X-ray crystallography and SAXS characterization, we demonstrate that PML RING tetramerizes through highly conserved PML-specific sequences, which are required for NB assembly and PML sumoylation. Conserved residues implicated in RING dimerization of other TRIMs also contribute to PML tetramer stability...
March 29, 2018: Nature Communications
Deneshia J McIntosh, Treniqka S Walters, Ifeanyi J Arinze, Jamaine Davis
BACKGROUND/AIMS: The transcription factor Nrf2 is a master regulator of the antioxidant defense system, protecting cells from oxidative damage. We previously reported that the SUMO-targeted E3 ubiquitin ligase (STUbL), RING finger protein 4 (RNF4) accelerated the degradation rate of Nrf2 in promyelocytic leukemia-nuclear body (PML-NB)-enriched fractions and decreased Nrf2-mediated gene transcription. The mechanisms that regulate Nrf2 nuclear levels are poorly understood. In this study, we aim to explore the role of the second mammalian STUbL, Arkadia/RNF111 on Nrf2...
March 23, 2018: Cellular Physiology and Biochemistry
Fang Yu, Guang Shi, Shimeng Cheng, Jiwei Chen, Shwu-Yuan Wu, Zhiqiang Wang, Nansong Xia, Yunhao Zhai, Zhenxing Wang, Yu Peng, Dong Wang, James X Du, Lujian Liao, Sheng-Zhong Duan, Tieliu Shi, Jinke Cheng, Cheng-Ming Chiang, Jiwen Li, Jiemin Wong
Regulation of transcription is fundamental to the control of cellular gene expression and function. Although recent studies have revealed a role for the oncoprotein MYC in amplifying global transcription, little is known as to how the global transcription is suppressed. Here we report that SUMO and MYC mediate opposite effects upon global transcription by controlling the level of CDK9 sumoylation. On one hand, SUMO suppresses global transcription via sumoylation of CDK9, the catalytic subunit of P-TEFb kinase essential for productive transcriptional elongation...
March 27, 2018: Cell Research
Therese C Rytz, Marcus J Miller, Fionn McLoughlin, Robert C Augustine, Richard S Marshall, Yu-Ting Juan, Yee-Yung Charng, Mark Scalf, Lloyd M Smith, Richard D Vierstra
The post-translational addition of Small Ubiquitin-Like Modifier (SUMO) is an essential protein modification in plants that provides protection against numerous environmental challenges. Ligation is accomplished by a small set of SUMO ligases, with the SAP-MIZ domain-containing SIZ1 and METHYL METHANESULFONATE-SENSITIVE 21 (MMS21) ligases having critical roles in stress protection and DNA endoreduplication/repair, respectively. To help identify their corresponding targets in Arabidopsis thaliana, we used siz1 and mms21 mutants for proteomic analyses of SUMOylated proteins enriched via an engineered SUMO1 isoform suitable for mass spectrometric studies...
March 27, 2018: Plant Cell
Huib Ovaa, Alfred C O Vertegaal
Ubiquitin (Ub) and ubiquitin-like (Ubl) proteins including small Ubl modifier (SUMO) are small proteins which are covalently linked to target proteins to regulate their functions. In this review, we discuss the current state of the art and point out what we feel this field urgently needs in order to delineate the wiring of the system. We discuss what is needed to unravel the connections between different components of the conjugation machineries for ubiquitylation and SUMOylation, and to unravel the connections between the conjugation machineries and their substrates...
March 27, 2018: Biochemical Society Transactions
Jian Bao, Min Qin, Yacoubou Abdoul Razak Mahaman, Bin Zhang, Fang Huang, Kuan Zeng, Yiyuan Xia, Dan Ke, Qun Wang, Rong Liu, Jian-Zhi Wang, Keqiang Ye, Xiaochuan Wang
Amyloid beta (Aβ) is a major pathological marker in Alzheimer's disease (AD), which is principally regulated by the rate-limiting β-secretase (i.e., BACE1) cleavage of amyloid precursor protein (APP). However, how BACE1 activity is posttranslationally regulated remains incompletely understood. Here, we show that BACE1 is predominantly SUMOylated at K501 residue, which escalates its protease activity and stability and subsequently increases Aβ production, leading to cognitive defect seen in the AD mouse model...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jingxuan Fu, Daoyuan Huang, Fuwen Yuan, Nan Xie, Qian Li, Xinpei Sun, Xuehong Zhou, Guodong Li, Tanjun Tong, Yu Zhang
DNA damage-induced NF-kB activation and the secretion of inflammatory cytokines play crucial roles in carcinogenesis and cellular senescence. However, the underlying mechanisms, especially the initial sensors and transducers connecting the nuclear DNA damage signal with cytoplasmic NF-kB activation remain incompletely understood. Here, we report that TRAF-interacting protein with forkhead-associated domain (TIFA), an established NF-kB activator in the cytosol, unexpectedly exhibited nuclear translocation and accumulation on damaged chromatin following genotoxic stress...
March 26, 2018: Journal of Biological Chemistry
Vijaykumar S Pawale, Prity Yadav, Rajendra P Roy
The post-translational conjugation of Small Ubiquitin like Modifier (SUMO) to target proteins occurs through a complex machinery that involves sequential action of at least three enzymes. SUMOylation performs crucial regulatory functions in several cellular processes. The availability of well-defined SUMO conjugates is necessary for untangling mechanistic of SUMOylation. However, assembly of homogeneous SUMO conjugates represent a challenge because of multi-step synthesis and unwieldiness of the reconstituted biosynthetic system...
March 25, 2018: Chembiochem: a European Journal of Chemical Biology
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