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https://www.readbyqxmd.com/read/29156803/tet1-inhibits-cell-proliferation-by-inducing-rassf5-expression
#1
Bo-Tai Li, Chao Yu, Ying Xu, Sheng-Bing Liu, Heng-Yu Fan, Wei-Wei Pan
Tet methylcytosine dioxygenases (TETs) catalyze the oxidative reactions of 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). However, TET1 roles in ovarian cancer cell growth are unknown. Here, we show that ectopic expression of TET1 increased 5hmC levels, and inhibited proliferation and colony formation in ovarian cancer cell lines. Furthermore, in vitro and in vivo functional studies demonstrated that TET1 overexpression is necessary for the suppression of ovarian cancer growth, whereas depletion of TET1 expression had the opposite effect...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156790/kaempferol-induces-autophagic-cell-death-of-hepatocellular-carcinoma-cells-via-activating-ampk-signaling
#2
Bing Han, Yi-Qun Yu, Qi-Lian Yang, Chun-Ying Shen, Xiao-Juan Wang
In the present study, we demonstrate that Kaempferol inhibited survival and proliferation of established human hepatocellular carcinoma (HCC) cell lines (HepG2, Huh-7, BEL7402, and SMMC) and primary human HCC cells. Kaempferol treatment in HCC cells induced profound AMP-activated protein kinase (AMPK) activation, which led to Ulk1 phosphorylation, mTOR complex 1 inhibition and cell autophagy. Autophagy induction was reflected by Beclin-1/autophagy gene 5 upregulation and p62 degradation as well as light chain 3B (LC3B)-I to LC3B-II conversion and LC3B puncta formation...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156706/mkrn3-functions-as-a-novel-ubiquitin-e3-ligase-to-inhibit-nptx1-during-puberty-initiation
#3
Huifang Liu, Xiangxin Kong, Fengling Chen
Central precocious puberty (CPP) is attributed to the disorder of some trigger factors those can activate the hypothalamic-pituitary-gonadal axis controlled by GnRH neurons. Many recent studies reveal one of those trigger factors, Makorin ring finger protein 3 (Mkrn3), whose loss-of-function mutations are implicated in CPP. Although Mkrn3 contained zinc Ring finger domain is considered as a putative E3 ubiquitin ligase, its actual function is never reported. Here, our results demonstrated that in mice hypothalamus before and when puberty initiated, Mkrn3 expressed the reversed tendency with Nptx1, which is an important secreted protein for neuron development...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156689/implications-of-pi3k-akt-inhibition-on-rest-protein-stability-and-neuroendocrine-phenotype-acquisition-in-prostate-cancer-cells
#4
Ruiqui Chen, Yinan Li, Ralph Buttyan, Xuesen Dong
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that arises as a consequence of rigorous androgen receptor (AR) pathway inhibition (ARPI) therapies. While the PI3K/AKT pathway has been investigated as a co-therapeutic target with ARPI for advanced PCa, whether this strategy can prevent tumor progression to t-NEPC remains unknown. Here, we report that PI3K/AKT inhibition alone reduces RE-1 silencing transcription factor (REST) protein expression and induces multiple NE markers in PCa cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155878/irhom2-is-essential-for-innate-immunity-to-rna-virus-by-antagonizing-er-and-mitochondria-associated-degradation-of-visa
#5
Wei-Wei Luo, Shu Li, Chen Li, Zhou-Qin Zheng, Pan Cao, Zhen Tong, Huan Lian, Su-Yun Wang, Hong-Bing Shu, Yan-Yi Wang
VISA (also known as MAVS, IPS-1 and Cardif) is an essential adaptor protein in innate immune response to RNA virus. The protein level of VISA is delicately regulated before and after viral infection to ensure the optimal activation and timely termination of innate antiviral response. It has been reported that several E3 ubiquitin ligases can mediate the degradation of VISA, but how the stability of VISA is maintained before and after viral infection remains enigmatic. In this study, we found that the ER-associated inactive rhomboid protein 2 (iRhom2) plays an essential role in mounting an efficient innate immune response to RNA virus by maintaining the stability of VISA through distinct mechanisms...
November 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29155548/site-selective-rna-splicing-nanozyme-dnazyme-and-rtcb-conjugates-on-a-gold-nanoparticle
#6
Jessica R Petree, Kevin Yehl, Kornelia Galior, Roxanne Glazier, Brendan Deal, Khalid Salaita
Modifying RNA through either splicing or editing is a fundamental biological process for creating protein diversity from the same genetic code. Developing novel chemical biology tools for RNA editing has potential to transiently edit genes and to provide a better understanding of RNA biochemistry. Current techniques used to modify RNA include the use of ribozymes, adenosine deaminase and tRNA endonucleases. Herein, we report a nanozyme that is capable of splicing of virtually any RNA stem-loop. This nanozyme is comprised of a gold nanoparticle functionalized with three enzymes: two catalytic DNA strands with ribonuclease function and an RNA ligase...
November 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29155430/engineering-peptide-ligase-specificity-by-proteomic-identification-of-ligation-sites
#7
Amy M Weeks, James A Wells
Enzyme-catalyzed peptide ligation is a powerful tool for site-specific protein bioconjugation, but stringent enzyme-substrate specificity limits its utility. We developed an approach for comprehensively characterizing peptide ligase specificity for N termini using proteome-derived peptide libraries. We used this strategy to characterize the ligation efficiency for >25,000 enzyme-substrate pairs in the context of the engineered peptide ligase subtiligase and identified a family of 72 mutant subtiligases with activity toward N-terminal sequences that were previously recalcitrant to modification...
November 20, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29155132/stiffening-of-flexible-sumo1-protein-upon-peptide-binding-analysis-with-anisotropic-network-model
#8
Ranja Sarkar
SUMO (small ubiquitin-like modifier) proteins interact with a large number of target proteins via a key regulatory event called sumoylation that encompasses activation, conjugation and ligation of SUMO proteins through specific E1, E2, and E3-type enzymes respectively. Single-molecule atomic force microscopic (AFM) experiments performed to unravel bound SUMO1 along its N-C termini direction reveal that E3-ligases (in the form of small peptides) increase mechanical stability (along the axis) of the flexible protein upon binding...
November 16, 2017: Mathematical Biosciences
https://www.readbyqxmd.com/read/29154825/the-scf-ubiquitin-ligase-slimb-controls-nerfin-1-turnover-in-drosophila
#9
Xiaohui Lin, Feng Wang, Yuanpei Li, Chaojun Zhai, Guiping Wang, Xiaoting Zhang, Yang Gao, Tao Yi, Dan Sun, Shian Wu
The C2H2 type zinc-finger transcription factor Nerfin-1 expresses dominantly in Drosophila nervous system and plays an important role in early axon guidance decisions and preventing neurons dedifferentiation. Recently, increasing reports indicated that INSM1 (homologue to nerfin-1 in mammals) is a useful marker for prognosis of neuroendocrine tumors. The dynamic expression of Nerfin-1 is regulated post-transcriptionally by multiple microRNAs; however, its post-translational regulation is still unclear. Here we showed that the protein turnover of Nerfin-1 is regulated by Slimb, the substrate adaptor of SCF(Slimb) ubiquitin ligase complex...
November 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29152152/association-of-genetic-variations-in-the-lipid-regulatory-pathway-genes-fbxw7-and-srebps-with-coronary-artery-disease-among-han-chinese-and-uygur-chinese-populations-in-xinjiang-china
#10
Asiya Abudesimu, Dilare Adi, Dilixiati Siti, Xiang Xie, Yi-Ning Yang, Xiao-Mei Li, Ying-Hong Wang, Yong-Tao Wang, Ya-Jie Meng, Fen Liu, Bang-Dang Chen, Xiang Ma, Zhen-Yan Fu, Yi-Tong Ma
Background: Hyperlipidemia is a major risk factor for coronary artery disease (CAD). The current study was designed to explore the possible correlation between single nucleotide polymorphisms (SNPs) in the lipid homeostasis regulatory genes F-box and WD repeat domain-containing 7 (FBXW7) and sterol regulatory element-binding proteins (SREBPs) with CAD among Han Chinese and Uygur Chinese populations in Xinjiang, China. Results: In the Uygur Chinese population, rs9902941 in SREBP-1 and rs10033601 in FBXW7 were found to be associated with CAD in a recessive model (TT vs...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150614/spatial-regulation-of-contractility-by-neuralized-and-bearded-during-furrow-invagination-in-drosophila
#11
Gantas Perez-Mockus, Khalil Mazouni, Vanessa Roca, Giulia Corradi, Vito Conte, François Schweisguth
Embryo-scale morphogenesis arises from patterned mechanical forces. During Drosophila gastrulation, actomyosin contractility drives apical constriction in ventral cells, leading to furrow formation and mesoderm invagination. It remains unclear whether and how mechanical properties of the ectoderm influence this process. Here, we show that Neuralized (Neur), an E3 ubiquitin ligase active in the mesoderm, regulates collective apical constriction and furrow formation. Conversely, the Bearded (Brd) proteins antagonize maternal Neur and lower medial-apical contractility in the ectoderm: in Brd-mutant embryos, the ventral furrow invaginates properly but rapidly unfolds as medial MyoII levels increase in the ectoderm...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29150431/the-e3-ubiquitin-ligase-apc-c-c-dh1-degrades-mcph1-after-mcph1-%C3%AE-trcp2-cdc25a-mediated-mitotic-entry-to-ensure-neurogenesis
#12
Xiaoqian Liu, Wen Zong, Tangliang Li, Yujun Wang, Xingzhi Xu, Zhong-Wei Zhou, Zhao-Qi Wang
Mutations of microcephalin (MCPH1) can cause the neurodevelopmental disorder primary microcephaly type 1. We previously showed that MCPH1 deletion in neural stem cells results in early mitotic entry that distracts cell division mode, leading to exhaustion of the progenitor pool. Here, we show that MCPH1 interacts with and promotes the E3 ligase βTrCP2 to degrade Cdc25A independent of DNA damage. Overexpression of βTrCP2 or the knockdown of Cdc25A remedies the high mitotic index and rescues the premature differentiation of Mcph1-deficient neuroprogenitors in vivo MCPH1 itself is degraded by APC/C(C)(dh1), but not APC/C(C)(dc20), in late mitosis and G1 phase...
November 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29149649/chk1-inhibitors-overcome-imatinib-resistance-in-chronic-myeloid-leukemia-cells
#13
Hu Lei, Jin Jin, Meng Liu, Xiangyun Li, Hao Luo, Li Yang, Hanzhang Xu, Yingli Wu
Drug resistance to tyrosine kinase inhibitors (TKIs) is currently a clinical problem of chronic myelogenous leukemia (CML). Bcr-Abl protein depletion is considered as a way to overcome drug resistance to TKIs. In our study, Chk1 inhibitors, AZD7762 and MK-8776, had strong antitumor effects on CML cell line KBM5 and imatinib-resistant form KBM5(T315I). Moreover, Chk1 inhibitors showed a strong cytotoxic effect on leukemia cells from primary CML and imatinib-resistance CML patients, but low cytotoxic effect on normal human mononuclear cells...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29149645/xylella-fastidiosa-induces-differential-expression-of-lignification-related-genes-and-lignin-accumulation-in-tolerant-olive-trees-cv-leccino
#14
Erika Sabella, Andrea Luvisi, Alessio Aprile, Carmine Negro, Marzia Vergine, Francesca Nicolì, Antonio Miceli, Luigi De Bellis
Recently, Xylella fastidiosa was reported in Italy, associated with the "Olive Quick Decline Syndrome". The cv. Leccino exhibits an evident tolerance with a slow disease progression compared with the other cultivars. Between the mechanisms proposed to explain the putative tolerance of some hosts to X. fastidiosa diseases, lignin deposition plays an important role. Analysis of phenolic compounds in healthy and infected Leccino and Cellina di Nardò leaves showed, in the two cultivars, a reduction of hydroxytyrosol glucoside (usually associated with drought and cold stress) and, only in Leccino, an increase of quinic acid, precursor of lignin...
November 10, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/29149406/role-and-fate-of-tctp-in-protein-degradative-pathways
#15
Michel Vidal
This chapter focuses on published studies specifically concerning TCTP and its involvement in degradation or stabilization of various proteins, and also in its own degradation in different ways. The first part relates to the inhibition of proteasomal degradation of proteins. This can be achieved by masking ubiquitination sites of specific partners, by favoring ubiquitin E3 ligase degradation, or by regulating proteasome activity. The second part addresses the ability of TCTP to favor degradation of specific proteins through proteasome or macroautophagic pathways...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149173/trade-off-and-flexibility-in-the-dynamic-regulation-of-the-cullin-ring-ubiquitin-ligase-repertoire
#16
Ronny Straube, Meera Shah, Dietrich Flockerzi, Dieter A Wolf
Cullin-RING ubiquitin ligases (CRLs) catalyze the ubiquitylation of substrates many of which are degraded by the 26S proteasome. Their modular architecture enables recognition of numerous substrates via exchangeable substrate receptors that competitively bind to a cullin scaffold with high affinity. Due to the plasticity of these interactions there is ongoing uncertainty how cells maintain a flexible CRL repertoire in view of changing substrate loads. Based on a series of in vivo and in vitro studies, different groups proposed that the exchange of substrate receptors is mediated by a protein exchange factor named Cand1...
November 17, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29148537/adenomatoid-tumors-of-the-male-and-female-genital-tract-are-defined-by-traf7-mutations-that-drive-aberrant-nf-kb-pathway-activation
#17
Benjamin Goode, Nancy M Joseph, Meredith Stevers, Jessica Van Ziffle, Courtney Onodera, Eric Talevich, James P Grenert, Iwei Yeh, Boris C Bastian, Joanna J Phillips, Karuna Garg, Joseph T Rabban, Charles Zaloudek, David A Solomon
Adenomatoid tumors are the most common neoplasm of the epididymis, and histologically similar adenomatoid tumors also commonly arise in the uterus and fallopian tube. To investigate the molecular pathogenesis of these tumors, we performed genomic profiling on a cohort of 31 adenomatoid tumors of the male and female genital tracts. We identified that all tumors harbored somatic missense mutations in the TRAF7 gene, which encodes an E3 ubiquitin ligase belonging to the family of tumor necrosis factor receptor-associated factors (TRAFs)...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29148103/extracytoplasmic-function-sigma-factor-%C3%AF-d-confers-resistance-to-environmental-stress-by-enhancing-mycolate-synthesis-and-modifying-peptidoglycan-structures-in-corynebacterium-glutamicum
#18
Koichi Toyoda, Inui Masayuki
Mycolates are α-branched, β-hydroxylated, long-chain fatty acid specifically synthesized in bacteria in the suborder Corynebacterineae of the phylum Actinobacteria. They form an outer membrane, which functions as a permeability barrier and confers pathogenic mycobacteria to resistance to antibiotics. Although the mycolate biosynthetic pathway has been intensively studied, knowledge of transcriptional regulation of genes involved in this pathway is limited. Here we report that the extracytoplasmic function sigma factor σ(D) is a key regulator of the mycolate synthetic genes in Corynebacterium glutamicum in the suborder...
November 17, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29147904/the-multifaceted-roles-of-dj-1-as-an-antioxidant
#19
Prahlad V Raninga, Giovanna Di Trapani, Kathryn F Tonissen
The DJ-1 protein was originally linked with Parkinson's disease and is now known to have antioxidant functions. The protein has three redox-sensitive cysteine residues, which are involved in its dimerisation and functional properties. A mildly oxidised form of DJ-1 is the most active form and protects cells from oxidative stress conditions. DJ-1 functions as an antioxidant through a variety of mechanisms, including a weak direct antioxidant activity by scavenging reactive oxygen species. DJ-1 also regulates a number of signalling pathways, including the inhibition of apoptosis signal-regulating kinase 1 (ASK1)-induced apoptosis under oxidative stress conditions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147007/modulating-cellular-balance-of-rps3-mono-ubiquitination-by-both-hel2-e3-ligase-and-ubp3-deubiquitinase-regulates-protein-quality-control
#20
Youjin Jung, Hag Dong Kim, Hee Woong Yang, Hye Jin Kim, Chang-Young Jang, Joon Kim
When a ribosome complex is stalled during the translation elongation process in eukaryotes, the mono-ubiquitination of Rps3 has recently been shown to be critical to ribosome quality control. We have discovered that the regulatory role of Rps3 mono-ubiquitination is controlled by a deubiquitinase. We also showed that an autophagic signal appears to be coupled to the mono-ubiquitination of Rps3p through the entrance of Ubp3p into the autophagosome in yeasts. The mono-ubiquitination of the Rps3 protein is tightly modulated by reciprocal action between the Hel2p E3 ligase and the Ubp3p deubiquitinase in yeasts and the reciprocal action between the RNF123 E3 ligase and the USP10 deubiquitinase in mammalian cells...
November 17, 2017: Experimental & Molecular Medicine
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