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Xianpeng Liu, Bo Zhao, Limin Sun, Karan Bhuripanyo, Yiyang Wang, Yingtao Bi, Ramana V Davuluri, Duc M Duong, Dhaval Nanavati, Jun Yin, Hiroaki Kiyokawa
Protein ubiquitination is mediated sequentially by ubiquitin activating enzyme E1, ubiquitin conjugating enzyme E2 and ubiquitin ligase E3. Uba1 was thought to be the only E1 until the recent identification of Uba6. To differentiate the biological functions of Uba1 and Uba6, we applied an orthogonal ubiquitin transfer (OUT) technology to profile their ubiquitination targets in mammalian cells. By expressing pairs of an engineered ubiquitin and engineered Uba1 or Uba6 that were generated for exclusive interactions, we identified 697 potential Uba6 targets and 527 potential Uba1 targets with 258 overlaps...
January 30, 2017: Nature Communications
Xingxin Wu, Xudong Wu, Yuxiang Ma, Fenli Shao, Yang Tan, Tao Tan, Liyun Gu, Yang Zhou, Beicheng Sun, Yang Sun, Xuefeng Wu, Qiang Xu
Excessive activation of hepatic stellate cells (HSCs) is a key step in liver fibrogenesis. Here we report that CUG-binding protein 1 (CUGBP1) expression is elevated in HSCs and positively correlates with liver fibrosis severity in human liver biopsies. Transforming growth factor-beta (TGF-β) selectively increases CUGBP1 expression in cultured HSCs in a p38 mitogen-activated protein kinase (MAPK)-dependent manner. Knockdown of CUGBP1 inhibits alpha smooth muscle actin (α-SMA) expression and promotes interferon gamma (IFN-γ) production in HSCs in vitro...
November 17, 2016: Nature Communications
Kui Zhai, Lei Gu, Zhiguang Yang, Yang Mao, Meng Jin, Yan Chang, Qi Yuan, Veronique Leblais, Huiwen Wang, Rodolphe Fischmeister, Guangju Ji
AIMS/HYPOTHESIS: CUG-binding protein 1 (CUGBP1) is a multifunctional RNA-binding protein that regulates RNA processing at several stages including translation, deadenylation and alternative splicing, as well as RNA stability. Recent studies indicate that CUGBP1 may play a role in metabolic disorders. Our objective was to examine its role in endocrine pancreas function through gain- and loss-of-function experiments and to further decipher the underlying molecular mechanisms. METHODS: A mouse model in which type 2 diabetes was induced by a high-fat diet (HFD; 60% energy from fat) and mice on a standard chow diet (10% energy from fat) were compared...
September 2016: Diabetologia
Bernd Rattenbacher, Daniel Beisang, Darin L Wiesner, Jonathan C Jeschke, Maximilian von Hohenberg, Irina A Vlasova-St Louis, Paul R Bohjanen
No abstract text is available yet for this article.
February 2016: Molecular and Cellular Biology
Xiaofei Wang, Wenjie Jiao, Yandong Zhao, Liangdong Zhang, Ruyong Yao, Yongjie Wang, Mingzhao Wang, Yiren Luo, Jinpeng Zhao
BACKGROUND: The brain is a frequent site of metastases from non-small cell lung cancer (NSCLC). The purpose of this study was to detect the expression of CUG-binding protein 1 (CUGBP1) messenger ribonucleic acid (mRNA) and Ki-67 in metastasized brain tissue from NSCLC and determine the relationship between CUGBP1 and brain metastases. METHODS: The expression of CUGBP1 mRNA and Ki-67 in metastasized brain tissue from NSCLC was investigated by semiquantitative polymerase chain reaction and immunohistochemistry, respectively...
January 2016: Thoracic Cancer
Liang Xia, Caixing Sun, Qinglin Li, Fang Feng, Enqi Qiao, Limin Jiang, Bin Wu, Minghua Ge
BACKGROUND: As a member of the CELF family, CELF1 (CUG-binding protein 1, CUGBP1) is involved in cardiac and embryonic development, skeletal muscle differentiation and mammary epithelial cell proliferation. CELF1 is also observed in many kinds of cancer and may play a great role in tumorigenesis and deterioration. However, the expression and mechanism of its function in human glioma remain unclear. METHODS: We examined CELF1 expression in 62 glioma patients by immunohistochemistry and Western blot...
2015: International Journal of Biological Sciences
Ting-Xi Yu, Bei-Lin Gu, Jun-Kai Yan, Jie Zhu, Wei-Hui Yan, Jie Chen, Lin-Xi Qian, Wei Cai
The effectiveness and stability of epithelial barrier depend on apical junctional complexes, which consist of tight junctions (TJs) and adherens junctions (AJs). E-cadherin is the primary component of AJs, and it is essential for maintenance of cell-to-cell interactions and regulates the epithelial barrier. However, the exact mechanism underlying E-cadherin expression, particularly at the posttranscriptional level, remains largely unknown. RNA-binding proteins CUG-binding protein 1 (CUGBP1) and HU antigen R (HuR) are highly expressed in the intestinal epithelial tissues and modulate the stability and translation of target mRNAs...
January 1, 2016: American Journal of Physiology. Cell Physiology
Longfei Yang, Jinlong Zhang, Jiajia Chen, Huricha Jin, Jian Liu, Shen Huang, Zhiming Cui
CUG-binding protein 1, a member of the CELF (CUGBP and embryonic lethal abnormal vision-like factor) family of RNA-binding proteins, is shown to be multifunctional, regulating many posttranscriptional processes including alternative splicing, deadenylation, mRNA decay, and translation. Recently, CUGBP1 is found to represses p27 IRES activity and inhibits expression of endogenous p27 in cultured breast cancer cells. However, the roles of CUGBP1 in central nervous system injury remain unknown. In our study, we performed acute spinal cord injury (SCI) model in adult rats in order to research the expression changes of CUGBP1 in spinal cord...
September 2015: Neurochemical Research
Takayuki Katoh, Hiroaki Hojo, Tsutomu Suzuki
MicroRNA-122 (miR-122), which is expressed at high levels in hepatocytes, is selectively stabilized by 3'-adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. Here, we report that poly(A)-specific ribonuclease (PARN) is responsible for the deadenylation and destabilization of miR-122. The 3'-oligoadenylated variant of miR-122 was detected in Huh7 cells when PARN was down-regulated. In addition, both the steady-state level and stability of miR-122 were increased in PARN knockdown cells. We also demonstrate that CUG-binding protein 1 (CUGBP1) specifically interacts with miR-122 and other UG-rich miRNAs, and promotes their destabilization...
September 3, 2015: Nucleic Acids Research
Meghan Breaux, Kyle Lewis, Leila Valanejad, Polina Iakova, Fengju Chen, Qianxing Mo, Estela Medrano, Lubov Timchenko, Nikolai Timchenko
The histone acetyltransferase p300 has been implicated in the regulation of liver biology; however, molecular mechanisms of this regulation are not known. In this paper, we examined these mechanisms using transgenic mice expressing a dominant negative p300 molecule (dnp300). While dnp300 mice did not show abnormal growth within 1 year, these mice have many alterations in liver biology and liver functions. We found that the inhibition of p300 leads to the accumulation of heterochromatin foci in the liver of 2-month-old mice...
September 1, 2015: Molecular and Cellular Biology
Liam D Tryon, Matthew J Crilly, David A Hood
The purpose of this study was to determine how the expression of mitochondrial transcription factor A (Tfam), a protein that governs mitochondrial DNA (mtDNA) transcription and replication, is regulated during a state of reduced organelle content imposed by muscle disuse. We measured Tfam expression at 8 h, 16 h, 24 h, 3 days, or 7 days following denervation and hypothesized that decreases in Tfam expression would precede mitochondrial loss. Muscle mass was lowered by 13% and 38% at 3 and 7 days postdenervation, while cytochrome c oxidase activity fell by 33% and 39% at the same time points...
August 15, 2015: American Journal of Physiology. Cell Physiology
Eric T Wang, Amanda J Ward, Jennifer M Cherone, Jimena Giudice, Thomas T Wang, Daniel J Treacy, Nicole J Lambert, Peter Freese, Tanvi Saxena, Thomas A Cooper, Christopher B Burge
RNA binding proteins of the conserved CUGBP1, Elav-like factor (CELF) family contribute to heart and skeletal muscle development and are implicated in myotonic dystrophy (DM). To understand their genome-wide functions, we analyzed the transcriptome dynamics following induction of CELF1 or CELF2 in adult mouse heart and of CELF1 in muscle by RNA-seq, complemented by crosslinking/immunoprecipitation-sequencing (CLIP-seq) analysis of mouse cells and tissues to distinguish direct from indirect regulatory targets...
June 2015: Genome Research
Thomas Beiter, Miriam Hoene, Frauke Prenzler, Frank C Mooren, Jürgen M Steinacker, Cora Weigert, Andreas M Nieß, Barbara Munz
The role of inflammation in skeletal muscle adaptation to exercise is complex and has hardly been elucidated so far. While the acute inflammatory response to exercise seems to promote skeletal muscle training adaptation and regeneration, persistent, low-grade inflammation, as seen in a multitude of chronic diseases, is obviously detrimental. The regulation of cytokine production in skeletal muscle cells has been relatively well studied, yet little is known about the compensatory and anti-inflammatory mechanisms that resolve inflammation and restore tissue homeostasis...
2015: Exercise Immunology Review
Lan Liu, Miao Ouyang, Jaladanki N Rao, Tongtong Zou, Lan Xiao, Hee Kyoung Chung, Jing Wu, James M Donahue, Myriam Gorospe, Jian-Ying Wang
The mammalian intestinal epithelium is one of the most rapidly self-renewing tissues in the body, and its integrity is preserved through strict regulation. The RNA-binding protein (RBP) ELAV-like family member 1 (CELF1), also referred to as CUG-binding protein 1 (CUGBP1), regulates the stability and translation of target mRNAs and is implicated in many aspects of cellular physiology. We show that CELF1 competes with the RBP HuR to modulate MYC translation and regulates intestinal epithelial homeostasis. Growth inhibition of the small intestinal mucosa by fasting in mice was associated with increased CELF1/Myc mRNA association and decreased MYC expression...
May 15, 2015: Molecular Biology of the Cell
Haijiao Lu, Zhuang Yu, Shihai Liu, Lianhua Cui, Xiaozheng Chen, Ruyong Yao
CUGBP1, which is involved in posttranscriptional regulatory networks, may control cell growth, activation and differentiation. Meanwhile, CCAAT/enhancer-binding protein α (C/EBPα) acts as a basic leucine zipper transcription factor which controls differentiation-dependent gene expression and inhibits cell proliferation. To date, very little is known about the association between CUGBP 1 and C/EBPα in regulating cell proliferation and apoptosis in non-small cell lung cancer (NSCLC). CUGBP1 and C/EBPα mRNA expressions were analyzed in NSCLC tumor and adjacent normal tissues, and the relationship in clinicopathological parameters was evaluated...
March 2015: Medical Oncology
Caihong Gao, Zhuang Yu, Shihai Liu, Hou Xin, Xiumei Li
The multifunctional RNA-binding protein CUGBP1 regulates multiple aspects of nuclear and cytoplasmic messenger RNA (mRNA) processing, including splicing, stabilization, and translation of mRNAs. Previous studies have shown that CUGBP1 is overexpressed in non-small-cell lung cancer (NSCLC) tissues, but the pathological functions of CUGBP1 in tumorigenesis and development are unknown. Here, we provide the first evidence demonstrating the clinicopathological significance of CUGBP1 in NSCLC. Using immunohistochemistry, the levels of CUGBP1 expression in NSCLC tissues and adjacent non-cancerous tissues were examined and determined to be associated with differentiation...
June 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Daniel Beisang, Cavan Reilly, Paul R Bohjanen
Alternative polyadenylation (APA) is an evolutionarily conserved mechanism for regulating gene expression. Transcript 3' end shortening through changes in polyadenylation site usage occurs following T cell activation, but the consequences of APA on gene expression are poorly understood. We previously showed that GU-rich elements (GREs) found in the 3' untranslated regions of select transcripts mediate rapid mRNA decay by recruiting the protein CELF1/CUGBP1. Using a global RNA sequencing approach, we found that a network of CELF1 target transcripts involved in cell division underwent preferential 3' end shortening via APA following T cell activation, resulting in decreased inclusion of CELF1 binding sites and increased transcript expression...
October 15, 2014: Gene
Yi Zhou, Hongzhi Ma, Jugao Fang, Meng Lian, Ling Feng, Ru Wang
To investigate the role of CUG-binding protein 1 (CUGBP1) in human laryngeal cancer, we employed lentivirus-mediated short hairpin RNA (shRNA) to knockdown CUGBP1 expression in Hep-2 cells. Depletion of CUGBP1 remarkably inhibited the proliferation of Hep-2 cells. CUGBP1 knockdown induced cell cycle arrest in S phase, especially in the sub-G1 phase, representing apoptotic cells. Knockdown of CUGBP1 in Hep-2 cells markedly increased the expression of LIP and cleavage of PARP, which could contribute to apoptosis...
December 2014: Cell Biology International
Christina Wei, Karlie Jones, Nikolai A Timchenko, Lubov Timchenko
Myotonic dystrophy type 1 (DM1), an incurable, neuromuscular disease, is caused by the expansion of CTG repeats within the 3' UTR of DMPK on chromosome 19q. In DM1 patients, mutant DMPK transcripts deregulate RNA metabolism by altering CUG RNA-binding proteins. Several approaches have been proposed for DM1 therapy focused on specific degradation of the mutant CUG repeats or on correction of RNA-binding proteins, affected by CUG repeats. One such protein is CUG RNA-binding protein (CUGBP1). The ability of CUGBP1 to increase or inhibit translation depends on phosphorylation at Ser302, which is mediated by cyclin D3-CDK4...
2013: Rare Diseases
Nicole Lambert, Alex Robertson, Mohini Jangi, Sean McGeary, Phillip A Sharp, Christopher B Burge
Specific protein-RNA interactions guide posttranscriptional gene regulation. Here, we describe RNA Bind-n-Seq (RBNS), a method that comprehensively characterizes sequence and structural specificity of RNA binding proteins (RBPs), and its application to the developmental alternative splicing factors RBFOX2, CELF1/CUGBP1, and MBNL1. For each factor, we recovered both canonical motifs and additional near-optimal binding motifs. RNA secondary structure inhibits binding of RBFOX2 and CELF1, while MBNL1 favors unpaired Us but tolerates C/G pairing in motifs containing UGC and/or GCU...
June 5, 2014: Molecular Cell
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