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https://www.readbyqxmd.com/read/28346425/chip-stub1-regulates-the-warburg-effect-by-promoting-degradation-of-pkm2-in-ovarian-carcinoma
#1
Y Shang, J He, Y Wang, Q Feng, Y Zhang, J Guo, J Li, S Li, Y Wang, G Yan, F Ren, Y Shi, J Xu, N Zeps, Y Zhai, D He, Z Chang
Tumor cells preferentially adopt aerobic glycolysis for their energy supply, a phenomenon known as the Warburg effect. It remains a matter of debate as to how the Warburg effect is regulated during tumor progression. Here, we show that CHIP (carboxyl terminus of Hsc70-interacting protein), a U-box E3 ligase, suppresses tumor progression in ovarian carcinomas by inhibiting aerobic glycolysis. While CHIP is downregulated in ovarian carcinoma, induced expression of CHIP results in significant inhibition of the tumor growth examined by in vitro and in vivo experiments...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28345606/53bp1-contributes-to-regulation-of-autophagic-clearance-of-mitochondria
#2
Cha Kyung Youn, Hong Beum Kim, Ting Ting Wu, Sanggon Park, Sung Il Cho, Jung-Hee Lee
Autophagy, the primary recycling pathway within cells, plays a critical role in mitochondrial quality control under normal growth conditions and in the cellular response to stress. Here we provide evidence that 53BP1, a DNA damage response protein, is involved in regulating mitochondrial clearance from the cell via a type of autophagy termed mitophagy. We found that when either human or mouse cells were 53BP1-deficient, there was an increase in mitochondrial abnormalities, as observed through staining intensity, aggregation, and increased mass...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345603/pja2-ubiquitinates-the-hiv-1-tat-protein-with-atypical-chain-linkages-to-activate-viral-transcription
#3
Tyler B Faust, Yang Li, Gwendolyn M Jang, Jeffrey R Johnson, Shumin Yang, Amit Weiss, Nevan J Krogan, Alan D Frankel
Transcription complexes that assemble at the HIV-1 promoter efficiently initiate transcription but generate paused RNA polymerase II downstream from the start site. The virally encoded Tat protein hijacks positive transcription elongation factor b (P-TEFb) to phosphorylate and activate this paused polymerase. In addition, Tat undergoes a series of reversible post-translational modifications that regulate distinct steps of the transcription cycle. To identify additional functionally important Tat cofactors, we performed RNAi knockdowns of sixteen previously identified Tat interactors and found that a novel E3 ligase, PJA2, ubiquitinates Tat in a non-degradative manner and specifically regulates the step of HIV transcription elongation...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345459/n6-isopentenyladenosine-promoted-hela-cell-apoptosis-through-inhibitions-of-akt-and-transforming-growth-factor-%C3%AE-activated-kinase-1-activation
#4
Miao Li, Yonghao Qi, Jing Wei, Lulu Lu, Xuan Zhao, Lijun Zhou
N6-Isopentenyladenosine, a member of the family of plant hormones, possesses anti-cancer activities on a number of cancer cell lines. However, its mode of action in cervical cancer cell remains poorly understood. Our computational docking studies showed that N6-Isopentenyladenosine could bind with the really interesting new gene domain of tumor necrosis factor receptor-associated factor 6, which is an ubiquitination E3 ligase. Tumor necrosis factor receptor-associated factor 6-mediated ubiquitination is known to activate both protein kinase B (also known as AKT) and transforming growth factor β-activated kinase 1, and the really interesting new gene domain comprises the core of the ubiquitin ligase catalytic domain...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28343913/sumoylation-inhibition-mediated-by-disruption-of-sumo-e1-e2-interactions-confers-plant-susceptibility-to-necrotrophic-fungal-pathogens
#5
Laura Castaño-Miquel, Abraham Mas, Inês Teixeira, Josep Seguí, Anna Perearnau, Bhagyasree N Thampi, Arnaldo L Schapire, Natalia Rodrigo, Gaelle La Verde, Silvia Manrique, Maria Coca, L Maria Lois
Protein modification by SUMO modulates essential biological processes in eukaryotes. SUMOylation is facilitated by sequential action of the E1-activating, E2-conjugating, and E3-ligase enzymes. In plants, SUMO regulates plant development and stress responses, which are key determinants in agricultural productivity. To generate additional tools for advancing our knowledge about the SUMO biology, we have developed a strategy for inhibiting in vivo SUMO conjugation based on disruption of SUMO E1-E2 interactions through expression of E1 SAE2(UFDCt) domain...
February 14, 2017: Molecular Plant
https://www.readbyqxmd.com/read/28340002/overexpression-of-the-rice-sumo-e3-ligase-gene-ossiz1-in-cotton-enhances-drought-and-heat-tolerance-and-substantially-improves-fiber-yields-in-the-field-under-reduced-irrigation-and-rainfed-conditions
#6
Neelam Mishra, Li Sun, Xunlu Zhu, Jennifer Smith, Anurag Prakash Srivastava, Xiaojie Yang, Necla Pehlivan, Nardana Esmaeili, Hong Luo, Guoxin Shen, Don Jones, Dick Auld, John Burke, Paxton Payton, Hong Zhang
The Arabidopsis SUMO E3 ligase gene AtSIZ1 plays important roles in plant response to abiotic stresses as loss of function in AtSIZ1 leads to increased sensitivity to drought, heat and salt stresses. Overexpression of the AtSIZ1 rice homolog, OsSIZ1, leads to increased heat and drought tolerance in bentgrass, suggesting that the function of the E3 ligase SIZ1 is highly conserved in plants and it plays a critical role in abiotic stress responses. To test the possibility that the SUMO E3 ligase could be used to engineer drought- and heat-tolerant crops, the rice gene OsSIZ1 was overexpressed in cotton...
March 1, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28338984/e3-ubiquitin-ligases-siah1-2-regulates-hypoxia-inducible-factor-1-hif1-mediated-th17-cell-differentiation
#7
Akiko Matsui-Hasumi, Yayoi Sato, Ayako Uto-Konomi, Satoshi Yamashita, Junji Uehori, Akihiko Yoshimura, Masakatsu Yamashita, Hiroshi Asahara, Shinobu Suzuki, Masato Kubo
IL-17 is known to be a cytokine mainly secreting from TH17 cells, which well associate with autoimmune inflammatory responses. In the generation of TH17 cells, RORc and RORa have pivotal roles in controlling the transcription of IL-17. We speculated additional regulation in IL-17A transcription and randomly screened a 6,344 clone cDNA library to identify specific modulators for IL-17A promoter activity. After the screen, the E3 ubiquitin ligases SIAH1 and SIAH2 were investigated further and confirmed to increase IL-17A promoter activity in T cell line and to promote TH17 development ex vivo...
March 17, 2017: International Immunology
https://www.readbyqxmd.com/read/28337377/the-e3-ubiquitin-ligase-chip-mir-92b-pten-regulatory-network-contributes-to-tumorigenesis-of-glioblastoma
#8
Tao Xu, Hongxiang Wang, Mei Jiang, Yong Yan, Weiqing Li, Hanchong Xu, Qilin Huang, Yicheng Lu, Juxiang Chen
Glioblastoma (GBM) is the most frequent, aggressive and fatal tumor in the central nervous system, while PTEN signaling is frequently deregulated in human GBM. We previously reported the up-regulation of the carboxyl terminal of Hsp70-interacting protein (CHIP) in GBM, however, the causal link between its dysregulation and tumorigenesis has not been established. Using miRNA microarrays and quantitative RT-PCR (qRT-PCR), we found activation of CHIP leads to increased transcription of miR-92b. Further studies in T98G and LN229 cells showed overexpression of miR-92b elicited reduction of PTEN and efficiently rescued glioma development in CHIP knock-down cells...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28337256/human-mesenchymal-stem-cell-homing-induced-by-skov3-cells
#9
Dongmei Fan, Xiaojuan Xie, Pengwei Qi, Xianan Yang, Ximeng Jin
Human mesenchymal stem cell (hMSC) homing is the migration of endogenous and exogenous hMSCS to the target organs and the subsequent colonization under the action chemotaxic factors. This is an important process involved in the repair of damaged tissues. However, we know little about the mechanism of hMSC homing. Stromal cell derived factor-1 (SDF-1) is a cytokine secreted by stromal cells. Its only receptor CXCR4 is widely expressed in blood cells, immune cells and cells in the central nervous system. SDF-1/CXCR4 signaling pathway plays an important role in hMSC homing and tissue repair...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28335430/a-review-on-ubiquitination-of-neurotrophin-receptors-facts-and-perspectives
#10
REVIEW
Julia Sánchez-Sánchez, Juan Carlos Arévalo
Ubiquitination is a reversible post-translational modification involved in a plethora of different physiological functions. Among the substrates that are ubiquitinated, neurotrophin receptors (TrkA, TrkB, TrkC, and p75(NTR)) have been studied recently. TrkA is the most studied receptor in terms of its ubiquitination, and different E3 ubiquitin ligases and deubiquitinases have been implicated in its ubiquitination, whereas not much is known about the other neurotrophin receptors aside from their ubiquitination...
March 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28335037/lrsam1-mediated-ubiquitylation-is-disrupted-in-axonal-charcot-marie-tooth-disease-2p
#11
Johanna E Hakonen, Vincenzo Sorrentino, Rossella Avagliano Trezza, Marit B de Wissel, Marlene van den Berg, Boris Bleijlevens, Fred van Ruissen, Ben Distel, Frank Baas, Noam Zelcer, Marian A J Weterman
Charcot-Marie-Tooth (CMT) disease type 2 is a genetically heterogeneous group of inherited neuropathies characterized by motor and sensory deficits as a result of peripheral axonal degeneration. We recently reported a frameshift mutation in the RING domain of LRSAM1 (c.2121_2122dup, p.Leu708Argfs) that encodes an E3 ubiquitin ligase, as the cause of axonal type CMT (CMT2P). However, the frequency of LRSAM1 mutations in CMT2 and the functional basis for their association with disease remains unknown. In this study we evaluated LRSAM1 mutations in two large Dutch cohorts...
March 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334804/a-critical-role-of-hrd1-in-the-regulation-of-optineurin-degradation-and-aggresome-formation
#12
Jiahui Mao, Qin Xia, Chunfeng Liu, Zheng Ying, Hongfeng Wang, Guanghui Wang
Mutations in optineurin (OPTN) are associated with several human disorders including amyotrophic lateral sclerosis (ALS) and primary open-angle glaucoma (POAG). OPTN is known to be a multifunctional autophagy receptor that plays important roles in NF-κB signaling, vesicle trafficking, maintenance of the Golgi apparatus and autophagy. Given that a loss of neurons and an abnormal aggregation of disease proteins are two key features of neurodegenerative diseases, protein quality control systems are considered to be tightly associated with neurodegeneration...
March 11, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334634/e3-ubiquitin-ligase-cbl-b-prevents-tumor-metastasis-by-maintaining-the-epithelial-phenotype-in-multiple-drug-resistant-gastric-and-breast-cancer-cells
#13
Ling Xu, Ye Zhang, Xiujuan Qu, Xiaofang Che, Tianshu Guo, Ying Cai, Aodi Li, Danni Li, Ce Li, Ti Wen, Yibo Fan, Kezuo Hou, Yanju Ma, Xuejun Hu, Yunpeng Liu
Multiple drug resistance (MDR) and metastasis are two major factors that contribute to the failure of cancer treatment. However, the relationship between MDR and metastasis has not been characterized. Additionally, the role of the E3 ubiquitin ligase Cbl-b in metastasis of MDR gastric and breast cancer is not well known. In the present study, we found that MDR gastric and breast cancer cells possess a typical mesenchymal phenotype and enhanced cell migration capacity. Additionally, Cbl-b is poorly expressed in MDR gastric and breast cancer cells...
March 20, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28330929/the-role-of-pias-sumo-e3-ligases-in-cancer
#14
REVIEW
Andrea Rabellino, Cristina Andreani, Pier Paolo Scaglioni
SUMOylation modifies the interactome, localization, activity, and lifespan of its target proteins. This process regulates several cellular machineries, including transcription, DNA damage repair, cell-cycle progression, and apoptosis. Accordingly, SUMOylation is critical in maintaining cellular homeostasis, and its deregulation leads to the corruption of a plethora of cellular processes that contribute to disease states. Among the proteins involved in SUMOylation, the protein inhibitor of activated STAT (PIAS) E3-ligases were initially described as transcriptional coregulators...
March 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28330927/e3-ubiquitin-ligase-ubr5-drives-the-growth-and-metastasis-of-triple-negative-breast-cancer
#15
Liqiu Liao, Mei Song, Xin Li, Lili Tang, Tuo Zhang, Lixing Zhang, Yihang Pan, Lotfi Chouchane, Xiaojing Ma
Patients with triple negative breast cancers (TNBC) are at high risk for recurrence and metastasis at an early time despite standard treatment, underscoring the need for novel therapeutic modalities. Here we report for the first time a distinctive and profound role of the E3 ubiquitin ligase UBR5 in the growth and metastasis of TNBC. An analysis of primary TNBC specimen by whole exon sequencing revealed strong gene amplifications of UBR5 associated with the disease. UBR5 overexpression in TNBC tissues was confirmed at mRNA and protein levels...
March 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28330622/dido-as-a-switchboard-that-regulates-self-renewal-and-differentiation-in%C3%A2-embryonic-stem-cells
#16
Agnes Fütterer, Jésus de Celis, Rosana Navajas, Luis Almonacid, Julio Gutiérrez, Amaia Talavera-Gutiérrez, Cristina Pacios-Bras, Ilenia Bernascone, Fernando Martin-Belmonte, Carlos Martinéz-A
Transition from symmetric to asymmetric cell division requires precise coordination of differential gene expression. We show that embryonic stem cells (ESCs) mainly express DIDO3 and that their differentiation after leukemia inhibitory factor withdrawal requires DIDO1 expression. C-terminal truncation of DIDO3 (Dido3ΔCT) impedes ESC differentiation while retaining self-renewal; small hairpin RNA-Dido1 ESCs have the same phenotype. Dido3ΔCT ESC differentiation is rescued by ectopic expression of DIDO3, which binds the Dido locus via H3K4me3 and RNA POL II and induces DIDO1 expression...
March 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28326016/early-origin-and-evolution-of-the-angelman-syndrome-ubiquitin-ligase-gene-ube3a
#17
REVIEW
Masaaki Sato
The human Ube3a gene encodes an E3 ubiquitin ligase and exhibits brain-specific genomic imprinting. Genetic abnormalities that affect the maternal copy of this gene cause the neurodevelopmental disorder Angelman syndrome (AS), which is characterized by severe mental retardation, speech impairment, seizure, ataxia and some unique behavioral phenotypes. In this review article, I highlight the evolution of the Ube3a gene and its imprinting to provide evolutionary insights into AS. Recent comparative genomic studies have revealed that Ube3a is most phylogenetically similar to HECTD2 among the human HECT (homologous to the E6AP carboxyl terminus) family of E3 ubiquitin ligases, and its distant evolutionary origin can be traced to common ancestors of fungi and animals...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28324045/ring-finger-protein-6-mediates-androgen-induced-granulosa-cell-proliferation-and-follicle-growth-via-modulation-of-androgen-receptor-signaling
#18
Jung Jin Lim, Chae Young Han, Dong Ryul Lee, Benjamin K Tsang
The destiny of the ovarian follicle (growth or atresia) is tightly regulated by actions and interactions of endocrine, paracrine and autocrine factors. Although androgens are known to be important in the regulation of folliculogenesis, whether they facilitate or suppress follicular growth has been controversial and the mechanisms involved are not fully understood. Moreover, the role and regulation of its receptor (AR) in mediating androgen signaling during follicular development is not clear. Here, we report that the active androgen dihydrotestosterone (DHT) up-regulates the expression of AR and its E3 ligase Ring Finger Protein 6 (RNF6), increasing site-specific AR polyubiquitination and AR transcriptional activity for sKit-L expression in preantral follicle growth...
January 30, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322991/thyroid-hormone-induce-a-p53-dependent-dna-damage-through-pi3k-akt-activation-in-sperm
#19
Hong Xian, Fang Wang, Wending Teng, Dong Yang, Ming Zhang
Accumulating evidences showed that thyroid hormone was participated in the functioning of the reproductive system, and an elevated level of thyroid hormones had a negative impact on reproductive system. However, the molecular basis for this observation still remains to be fully understood. Here, we show that l-Thyroxine significantly impaired human sperm motility. The molecular basis showed that thyroxine receptor stimulation triggers Phosphatidyl Inositol 3-kinase (PI3K)/Akt signaling activation leading to the E3 ligase MDM2 phosphorylation at serine 166, which directly interacted with p53 for degradation...
March 16, 2017: Gene
https://www.readbyqxmd.com/read/28322826/apc-cdh1-controls-cell-cycle-entry-during-liver-regeneration
#20
Ranran Cheng, Xin Liang, Quancheng Zhao, Zhusheng Lian, Lichun Tang, Chen Qiu, Huan Chen, Pumin Zhang
Cdh1 is one of the two adaptor proteins of anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase controlling mitosis and DNA replication. To date, the in vivo functions of Cdh1 have not been fully explored. In order to characterize Cdh1 in liver regeneration, we generated a conditional knock-out mouse model. Our data showed that loss of Cdh1 leads to increased and extended S phase progression possibly due to the upregulation of cyclin D1. Moreover, the increased DNA replication resulted in activated DNA damage response...
March 18, 2017: Experimental Cell Research
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