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Sudha Rajderkar, Christopher Panaretos, Vesa Kaartinen
Embryonic stem cells (ESCs) are an established model for investigating developmental processes, disease conditions, tissue regeneration and therapeutic targets. Previous studies have shown that tripartite motif-containing 33 protein (Trim33) functions as a chromatin reader during Nodal-induced mesoderm induction. Here we report that despite reduced proliferation, mouse ESCs deficient in Trim33 remained pluripotent when cultured under non-differentiating conditions. However, when induced to differentiate to embryoid bodies (EBs), the mutant cultures showed increased cell shedding and apoptosis at day 3 of differentiation...
December 2017: Biochemistry and Biophysics Reports
Xiaojie Xia, Feifei Zuo, Maoguo Luo, Ye Sun, Jianbo Bai, Qiaoran Xi
Tripartite motif 33 (TRIM33), a member of the transcription intermediate factor 1 (TIF1) family of transcription cofactors, mediates transforming growth factor-beta (TGF-β) signaling through its PHD-Bromo cassette in mesendoderm differentiation during early mouse embryonic development. However, the role of the TRIM33 RING domain in embryonic differentiation is less clear. Here, we report that TRIM33 mediates Wnt signaling by directly regulating the expression of a specific subset of Wnt target genes, and this action is independent of its RING domain...
August 24, 2017: Science China. Life Sciences
Doris Lou Demy, Muriel Tauzin, Mylène Lancino, Véronique le Cabec, Michael Redd, Emi Murayama, Isabelle Maridonneau-Parini, Nikolaus Trede, Philippe Herbomel
Macrophages infiltrate and establish in developing organs from an early stage, often before these have become vascularised. Similarly, leukocytes in general can quickly migrate through tissues to any site of wounding. This unique capacity is rooted in their characteristic amoeboid motility, the genetic basis of which is poorly known. Trim33 (Tif1-γ), a nuclear protein that associates with specific DNA binding transcription factors to modulate gene expression, has been found mainly involved in hematopoiesis and gene regulation by TGF-ß...
July 19, 2017: Journal of Cell Science
B Scholtissek, S Ferring-Schmitt, J Maier, J Wenzel
Dermatomyositis (DM) is an autoimmune disorder associated with a dysregulation of immune homeostasis of both the innate and adaptive immune system. Earlier data suggested that these two arms of the immune system interconnect in DM. In the current study, we analysed the association of autoantigen expression [adaptive system components: Mi2, transcriptional intermediary factor (TIF)1γ, small ubiquitin-like modifier 1 activating enzyme subunit (SAE)1, melanoma differentiation-associated protein (MDA)5] with markers of cellular stress (innate system components: MxA, p53) in skin and muscle (immunohistology and gene expression data, respectively)...
August 2017: Clinical and Experimental Dermatology
Sachiko Arai, Kenji Kita, Azusa Tanimoto, Shinji Takeuchi, Koji Fukuda, Hiroshi Sato, Seiji Yano
Rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) accounts for approximately 1-2% of all NSCLCs. To date, RET fusions that involve at least six fusion partners in NSCLC, such as KIF5B, CCDC6, NCOA4, TRIM33, CLIP1, and ERC1, have been identified. Recent clinical trials for RET fusion-positive NSCLC using vandetanib or cabozantinib demonstrated positive clinical response and considerable differential activities for RET inhibitors among fusion partners. Alectinib, an approved ALK inhibitor, is reported to inhibit KIF5B-RET and CCDC6-RET...
May 16, 2017: Oncotarget
Jia Guo, Wei Qin, Quan Xing, Manman Gao, Fuxin Wei, Zhi Song, Lingling Chen, Ying Lin, Xianling Gao, Zhengmei Lin
Tripartite motif containing 33 (TRIM33) functions both as a positive and negative regulator of the TGF-β/BMP pathway in tumors; however, its effect and mechanism during osteoblast proliferation and differentiation, which involves the TGF-β/BMP pathway is not defined. In this study, we used mouse C3H10T1/2 mesenchymal stem cell line and MC3T3-E1 preosteoblasts to investigate the role of TRIM33 during this process. The results demonstrated that the expression of TRIM33 increased during the differentiation. Moreover, the overexpression or knockdown of TRIM33 resulted in both an augmentation or decrease in osteoblast differentiation, which were measured by the expression of alkaline phosphatase (ALP) at the mRNA level, both Runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) at the protein level, and the formation of mineral modules...
November 2017: Journal of Cellular Physiology
Anne-Sophie Gallouet, Federica Ferri, Vanessa Petit, Aude Parcelier, Daniel Lewandowski, Nathalie Gault, Vilma Barroca, Stéphanie Le Gras, Eric Soler, Frank Grosveld, Irwin Davidson, Paul-Henri Romeo
The tripartite motif (TRIM) family of proteins plays important roles in innate immunity and antimicrobial infection. None of these proteins has been shown to directly regulate transcription of genes in monocyte/macrophage except TRIM33 that we have recently shown to be a macrophage specific transcriptional inhibitor of Ifnb1. Using ChIP-seq analyses, we now report that TRIM33 is bound to two fold more genes in immature than in mature myeloid cell lines. When located near the same genes, TRIM33 is bound to different sequences in the two cell lines suggesting a role of TRIM33 in both immature and mature myeloid cells...
January 17, 2017: Oncotarget
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
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
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
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
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
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
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
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
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
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
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
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
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
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