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https://www.readbyqxmd.com/read/27555324/a-novel-role-of-chromodomain-protein-cbx8-in-dna-damage-response
#1
Jay Oza, Bratati Ganguly, Atul Kulkarni, Vasudeva Ginjala, Ming Yao, Shridar Ganesan
Induction of DNA damage induces a dynamic repair process involving DNA repair factors and epigenetic regulators. Chromatin alterations must occur for DNA repair factors to gain access to DNA lesions and restore original chromatin configuration to preserve the gene expression profile. We characterize the novel role of CBX8, a chromodomain-containing protein with established roles in epigenetic regulation in DNA damage response. CBX8 protein rapidly accumulates at the sites of DNA damage within 30 s and progresses to accumulate until 4 min before gradually dispersing back to its predamage distribution by 15 min...
October 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27432991/loss-of-trim33-causes-resistance-to-bet-bromodomain-inhibitors-through-myc-and-tgf-%C3%AE-dependent-mechanisms
#2
Xiarong Shi, Valia T Mihaylova, Leena Kuruvilla, Fang Chen, Stephen Viviano, Massimiliano Baldassarre, David Sperandio, Ruben Martinez, Peng Yue, Jamie G Bates, David G Breckenridge, Joseph Schlessinger, Benjamin E Turk, David A Calderwood
Bromodomain and extraterminal domain protein inhibitors (BETi) hold great promise as a novel class of cancer therapeutics. Because acquired resistance typically limits durable responses to targeted therapies, it is important to understand mechanisms by which tumor cells adapt to BETi. Here, through pooled shRNA screening of colorectal cancer cells, we identified tripartite motif-containing protein 33 (TRIM33) as a factor promoting sensitivity to BETi. We demonstrate that loss of TRIM33 reprograms cancer cells to a more resistant state through at least two mechanisms...
August 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27130375/trim33-tif1%C3%AE-is-involved-in-late-stages-of-granulomonopoiesis-in-mice
#3
Marie-Lorraine Chrétien, Caroline Legouge, Romain Z Martin, Arlette Hammann, Malika Trad, Romain Aucagne, Anne Largeot, Jean-Noël Bastie, Laurent Delva, Ronan Quéré
Trim33/Tif1γ (Trim33) is a member of the tripartite motif family. Using a conditional hematopoietic-specific Trim33 knock-out (Trim33(Δ/Δ)) mouse, we showed previously that Trim33 deficiency in hematopoietic stem cells leads to severe defects in hematopoiesis, resembling the main features of human chronic myelomonocytic leukemia. We also demonstrated that Trim33 is involved in hematopoietic aging through TGFβ signaling. Nevertheless, how Trim33 contributes to the terminal stages of myeloid differentiation remains to be clarified...
August 2016: Experimental Hematology
https://www.readbyqxmd.com/read/26624618/trim33-binds-and-silences-a-class-of-young-endogenous-retroviruses-in-the-mouse-testis-a-novel-component-of-the-arms-race-between-retrotransposons-and-the-host-genome
#4
Luke Isbel, Rahul Srivastava, Harald Oey, Alex Spurling, Lucia Daxinger, Hamsa Puthalakath, Emma Whitelaw
Transposable elements (TEs) have been active in the mammalian genome for millions of years and the silencing of these elements in the germline is important for the survival of the host. Mice carrying reporter transgenes can be used to model transcriptional silencing. A mutagenesis screen for modifiers of epigenetic gene silencing produced a line with a mutation in Trim33; the mutants displayed increased expression of the reporter transgene. ChIP-seq of Trim33 in testis revealed 9,109 peaks, mostly at promoters...
December 2015: PLoS Genetics
https://www.readbyqxmd.com/read/26592194/trim33-switches-off-ifnb1-gene-transcription-during-the-late-phase-of-macrophage-activation
#5
Federica Ferri, Aude Parcelier, Vanessa Petit, Anne-Sophie Gallouet, Daniel Lewandowski, Marion Dalloz, Anita van den Heuvel, Petros Kolovos, Eric Soler, Mario Leonardo Squadrito, Michele De Palma, Irwin Davidson, Germain Rousselet, Paul-Henri Romeo
Despite its importance during viral or bacterial infections, transcriptional regulation of the interferon-β gene (Ifnb1) in activated macrophages is only partially understood. Here we report that TRIM33 deficiency results in high, sustained expression of Ifnb1 at late stages of toll-like receptor-mediated activation in macrophages but not in fibroblasts. In macrophages, TRIM33 is recruited by PU.1 to a conserved region, the Ifnb1 Control Element (ICE), located 15 kb upstream of the Ifnb1 transcription start site...
2015: Nature Communications
https://www.readbyqxmd.com/read/25984715/impact-of-adenovirus-e4-orf3-oligomerization-and-protein-localization-on-cellular-gene-expression
#6
Elizabeth I Vink, Yueting Zheng, Rukhsana Yeasmin, Thomas Stamminger, Laurie T Krug, Patrick Hearing
The Adenovirus E4-ORF3 protein facilitates virus replication through the relocalization of cellular proteins into nuclear inclusions termed tracks. This sequestration event disrupts antiviral properties associated with target proteins. Relocalization of Mre11-Rad50-Nbs1 proteins prevents the DNA damage response from inhibiting Ad replication. Relocalization of PML and Daxx impedes the interferon-mediated antiviral response. Several E4-ORF3 targets regulate gene expression, linking E4-ORF3 to transcriptional control...
May 2015: Viruses
https://www.readbyqxmd.com/read/25919951/the-transcriptional-cofactor-trim33-prevents-apoptosis-in-b-lymphoblastic-leukemia-by-deactivating-a-single-enhancer
#7
Eric Wang, Shinpei Kawaoka, Jae-Seok Roe, Junwei Shi, Anja F Hohmann, Yali Xu, Anand S Bhagwat, Yutaka Suzuki, Justin B Kinney, Christopher R Vakoc
Most mammalian transcription factors (TFs) and cofactors occupy thousands of genomic sites and modulate the expression of large gene networks to implement their biological functions. In this study, we describe an exception to this paradigm. TRIM33 is identified here as a lineage dependency in B cell neoplasms and is shown to perform this essential function by associating with a single cis element. ChIP-seq analysis of TRIM33 in murine B cell leukemia revealed a preferential association with two lineage-specific enhancers that harbor an exceptional density of motifs recognized by the PU...
April 28, 2015: ELife
https://www.readbyqxmd.com/read/25639486/tumour-suppressor-trim33-targets-nuclear-%C3%AE-catenin-degradation
#8
Jianfei Xue, Yaohui Chen, Yamei Wu, Zhongyong Wang, Aidong Zhou, Sicong Zhang, Kangyu Lin, Kenneth Aldape, Sadhan Majumder, Zhimin Lu, Suyun Huang
Aberrant activation of β-catenin in the nucleus has been implicated in a variety of human cancers, but the fate of nuclear β-catenin is unknown. Here we demonstrate that the tripartite motif-containing protein 33 (TRIM33), acting as an E3 ubiquitin ligase, reduces the abundance of nuclear β-catenin protein. TRIM33-mediated β-catenin is destabilized and is GSK-3β or β-TrCP independent. TRIM33 interacts with and ubiquitylates nuclear β-catenin. Moreover, protein kinase Cδ, which directly phosphorylates β-catenin at Ser715, is required for the TRIM33-β-catenin interaction...
2015: Nature Communications
https://www.readbyqxmd.com/read/25523394/tak1-smad4-and-trim33-redundantly-mediate-tgf-%C3%AE-3-signaling-during-palate-development
#9
Jamie Lane, Kenji Yumoto, Mohamad Azhar, Jun Ninomiya-Tsuji, Maiko Inagaki, Yingling Hu, Chu-Xia Deng, Jieun Kim, Yuji Mishina, Vesa Kaartinen
Transforming growth factor-beta3 (TGF-β3) plays a critical role in palatal epithelial cells by inducing palatal epithelial fusion, failure of which results in cleft palate, one of the most common birth defects in humans. Recent studies have shown that Smad-dependent and Smad-independent pathways work redundantly to transduce TGF-β3 signaling in palatal epithelial cells. However, detailed mechanisms by which this signaling is mediated still remain to be elucidated. Here we show that TGF-β activated kinase-1 (Tak1) and Smad4 interact genetically in palatal epithelial fusion...
February 15, 2015: Developmental Biology
https://www.readbyqxmd.com/read/25381221/mir-629-targets-trim33-to-promote-tgf%C3%AE-smad-signaling-and-metastatic-phenotypes-in-ccrcc
#10
Kentaro Jingushi, Yuko Ueda, Kaori Kitae, Hiroaki Hase, Hiroshi Egawa, Ikumi Ohshio, Ryoji Kawakami, Yuri Kashiwagi, Yohei Tsukada, Takumi Kobayashi, Wataru Nakata, Kazutoshi Fujita, Motohide Uemura, Norio Nonomura, Kazutake Tsujikawa
UNLABELLED: Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney, and clear cell RCC (ccRCC) represents its most common histological subtype. To identify a therapeutic target for ccRCC, miRNA expression signatures from ccRCC clinical specimens were analyzed. miRNA microarray and real-time PCR analyses revealed that miR-629 expression was significantly upregulated in human ccRCC compared with adjacent noncancerous renal tissue. Functional inhibition of miR-629 by a hairpin miRNA inhibitor suppressed ccRCC cell motility and invasion...
March 2015: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/25172487/the-e3-ubiquitin-ligase-tripartite-motif-33-is-essential-for-cytosolic-rna-induced-nlrp3-inflammasome-activation
#11
Leiyun Weng, Hiroki Mitoma, Coline Trichot, Coline Tricot, Musheng Bao, Ying Liu, Zhiqiang Zhang, Yong-Jun Liu
NLRP3 is a key component of caspase-activating macromolecular protein complexes called inflammasomes. It has been found that DHX33 is a cytosolic dsRNA sensor for the NLRP3 inflammasome, which induces caspase-1-dependent production of IL-1β and IL-18 upon activation. However, how the cytosolic dsRNAs induce the interaction between DHX33 and the NLRP3 inflammasome remains unknown. In this study, we report that TRIM33, a member of the tripartite motif (TRIM) family, can bind DHX33 directly and induce DHX33 ubiquitination via the lysine 218 upon dsRNA stimulation...
October 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/24959375/imbalanced-expression-of-tif1%C3%AE-inhibits-pancreatic-ductal-epithelial-cell-growth
#12
Martin Ligr, Xinyu Wu, Garrett Daniels, David Zhang, Huamin Wang, Cristina Hajdu, Jinhua Wang, Ruimin Pan, Zhiheng Pei, Lanjing Zhang, Marcovalerio Melis, Matthew R Pincus, John K Saunders, Peng Lee, Ruliang Xu
Transcriptional intermediary factor 1 gamma (Tif1γ) (Ectodermin/PTC7/RFG7/TRIM33) is a transcriptional cofactor with an important role in the regulation of the TGFβ pathway. It has been suggested that it competes with Smad2/Smad3 for binding to Smad4, or alternatively that it may target Smad4 for degradation, although its role in carcinogenesis is unclear. In this study, we showed that Tif1γ interacts with Smad1/Smad4 complex in vivo, using both yeast two-hybrid and coimmunoprecipitation assays. We demonstrated that Tif1γ inhibits transcriptional activity of the Smad1/Smad4 complex through its PHD domain or bromo-domainin pancreatic cells by luciferase assay...
2014: American Journal of Cancer Research
https://www.readbyqxmd.com/read/24881051/new-gene-evolution-in-the-bonus-tif1-%C3%AE-trim33-family-impacted-the-architecture-of-the-vertebrate-dorsal-ventral-patterning-network
#13
Robert G Wisotzkey, Janine C Quijano, Michael J Stinchfield, Stuart J Newfeld
Uncovering how a new gene acquires its function and understanding how the function of a new gene influences existing genetic networks are important topics in evolutionary biology. Here, we demonstrate nonconservation for the embryonic functions of Drosophila Bonus and its newest vertebrate relative TIF1-γ/TRIM33. We showed previously that TIF1-γ/TRIM33 functions as an ubiquitin ligase for the Smad4 signal transducer and antagonizes the Bone Morphogenetic Protein (BMP) signaling network underlying vertebrate dorsal-ventral axis formation...
September 2014: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/24425785/genomic-analysis-of-head-and-neck-squamous-cell-carcinoma-cell-lines-and-human-tumors-a-rational-approach-to-preclinical-model-selection
#14
Hua Li, John S Wawrose, William E Gooding, Levi A Garraway, Vivian Wai Yan Lui, Noah D Peyser, Jennifer R Grandis
UNLABELLED: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide. The increasing amount of genomic information on human tumors and cell lines provides more biologic data to design preclinical studies. We and others previously reported whole-exome sequencing data of 106 HNSCC primary tumors. In 2012, high-throughput genomic data and pharmacologic profiling of anticancer drugs of hundreds of cancer cell lines were reported. Here, we compared the genomic data of 39 HNSCC cell lines with the genomic findings in 106 HNSCC tumors...
April 2014: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/24189344/common-genetic-variants-on-1p13-2-associate-with-risk-of-autism
#15
K Xia, H Guo, Z Hu, G Xun, L Zuo, Y Peng, K Wang, Y He, Z Xiong, L Sun, Q Pan, Z Long, X Zou, X Li, W Li, X Xu, L Lu, Y Liu, Y Hu, D Tian, L Long, J Ou, Y Liu, X Li, L Zhang, Y Pan, J Chen, H Peng, Q Liu, X Luo, W Su, L Wu, D Liang, H Dai, X Yan, Y Feng, B Tang, J Li, Z Miedzybrodzka, J Xia, Z Zhang, X Luo, X Zhang, D St Clair, J Zhao, F Zhang
Autism is a highly heritable neurodevelopmental disorder, and known genetic variants, mostly rare, account only for a small proportion of cases. Here we report a genome-wide association study on autism using two Chinese cohorts as gene discovery (n=2150) and three data sets of European ancestry populations for replication analysis of top association signals. Meta-analysis identified three single-nucleotide polymorphisms, rs936938 (P=4.49 × 10(-8)), non-synonymous rs6537835 (P=3.26 × 10(-8)) and rs1877455 (P=8...
November 2014: Molecular Psychiatry
https://www.readbyqxmd.com/read/24015922/differential-cellular-gene-expression-in-duck-trachea-infected-with-a-highly-or-low-pathogenic-h5n1-avian-influenza-virus
#16
Pascale Massin, Claire Deleage, Aurélie Oger, François-Xavier Briand, Hélène Quenault, Yannick Blanchard
BACKGROUND: Avian influenza A (AI) viruses of subtypes H5 can cause serious disease outbreaks in poultry including panzootic due to H5N1 highly pathogenic (HP) viruses. These viruses are a threat not only for animal health but also public health due to their zoonotic potential. The domestic duck plays a major role in the epidemiological cycle of influenza virus subtypes H5 but little is known concerning host/pathogen interactions during influenza infection in duck species. In this study, a subtracted library from duck trachea (a primary site of influenza virus infection) was constructed to analyse and compare the host response after a highly or low pathogenic (LP) H5N1-infection...
2013: Virology Journal
https://www.readbyqxmd.com/read/23926104/tripartite-motif-containing-33-trim33-protein-functions-in-the-poly-adp-ribose-polymerase-parp-dependent-dna-damage-response-through-interaction-with-amplified-in-liver-cancer-1-alc1-protein
#17
Atul Kulkarni, Jay Oza, Ming Yao, Honeah Sohail, Vasudeva Ginjala, Antonia Tomas-Loba, Zuzana Horejsi, Antoinette R Tan, Simon J Boulton, Shridar Ganesan
Activation of poly(ADP-ribose) polymerase (PARP) near sites of DNA breaks facilitates recruitment of DNA repair proteins and promotes chromatin relaxation in part through the action of chromatin-remodeling enzyme Amplified in Liver Cancer 1 (ALC1). Through proteomic analysis we find that ALC1 interacts after DNA damage with Tripartite Motif-containing 33 (TRIM33), a multifunctional protein implicated in transcriptional regulation, TGF-β signaling, and tumorigenesis. We demonstrate that TRIM33 is dynamically recruited to DNA damage sites in a PARP1- and ALC1-dependent manner...
November 8, 2013: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/23777392/genetic-parameters-and-across-line-snp-associations-differ-for-natural-antibody-isotypes-igm-and-igg-in-laying-hens
#18
Y Sun, F Biscarini, H Bovenhuis, H K Parmentier, J J van der Poel
In an earlier study, serum levels of natural antibody isotypes IgM- and IgG-binding keyhole limpet hemocyanin were found to be indicative for survival through the laying period of hens and therefore considered as promising traits for future implementation in breeding programs for higher survival of layers. In the present study, we first estimated the genetic parameters for the two isotypes at 20, 40 and 65 weeks of age (IgM20, IgM40 and IgM65; IgG20, IgG40 and IgG65). Pooled genetic parameters were estimated from the total population of 2504 hens from nine purebred layer lines, with line included in the model to account for admixture...
August 2013: Animal Genetics
https://www.readbyqxmd.com/read/23765158/smad4-and-trim33-tif1%C3%AE-redundantly-regulate-neural-stem-cells-in-the-developing-cortex
#19
Sven Falk, Esméé Joosten, Vesa Kaartinen, Lukas Sommer
During central nervous system (CNS) development, proliferation and differentiation of neural stem cells (NSCs) have to be regulated in a spatio-temporal fashion. Here, we report different branches of the transforming growth factor β (TGFβ) signaling pathway to be required for the brain area-specific control of NSCs. In the midbrain, canonical TGFβ signaling via Smad4 regulates the balance between proliferation and differentiation of NSCs. Accordingly, Smad4 deletion resulted in horizontal expansion of NSCs due to increased proliferation, decreased differentiation, and decreased cell cycle exit...
November 2014: Cerebral Cortex
https://www.readbyqxmd.com/read/23533264/response-to-cabozantinib-in-patients-with-ret-fusion-positive-lung-adenocarcinomas
#20
Alexander Drilon, Lu Wang, Adnan Hasanovic, Yoshiyuki Suehara, Doron Lipson, Phil Stephens, Jeffrey Ross, Vincent Miller, Michelle Ginsberg, Maureen F Zakowski, Mark G Kris, Marc Ladanyi, Naiyer Rizvi
The discovery of RET fusions in lung cancers has uncovered a new therapeutic target for patients whose tumors harbor these changes. In an unselected population of non-small cell lung carcinomas (NSCLCs), RET fusions are present in 1% to 2% of cases. This incidence increases substantially, however, in never-smokers with lung adenocarcinomas that lack other known driver oncogenes. Although preclinical data provide experimental support for the use of RET inhibitors in the treatment of RET fusion-positive tumors, clinical data on response are lacking...
June 2013: Cancer Discovery
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