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Kap1/trim28

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https://www.readbyqxmd.com/read/27845900/trim28-multi-domain-protein-regulates-cancer-stem-cell-population-in-breast-tumor-development
#1
Patrycja Czerwińska, Parantu K Shah, Katarzyna Tomczak, Marta Klimczak, Sylwia Mazurek, Barbara Sozańska, Przemysław Biecek, Konstanty Korski, Violetta Filas, Andrzej Mackiewicz, Jannik N Andersen, Maciej Wiznerowicz
The expression of Tripartite motif-containing protein 28 (TRIM28)/Krüppel-associated box (KRAB)-associated protein 1 (KAP1), is elevated in at least 14 tumor types, including solid and hematopoietic tumors. High level of TRIM28 is associated with triple-negative subtype of breast cancer (TNBC), which shows higher aggressiveness and lower survival rates. Interestingly, TRIM28 is essential for maintaining the pluripotent phenotype in embryonic stem cells. Following on that finding, we evaluated the role of TRIM28 protein in the regulation of breast cancer stem cells (CSC) populations and tumorigenesis in vitro and in vivo...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27795446/transcriptional-silencing-of-moloney-murine-leukemia-virus-in-human-embryonic-carcinoma-cells
#2
Gary Z Wang, Stephen P Goff
: Embryonic carcinoma (EC) cells are malignant counterparts of embryonic stem (ES) cells and serve as useful models for investigating cellular differentiation and human embryogenesis. Though the susceptibility of murine EC cells to retroviral infection has been extensively analyzed, few studies of retrovirus infection of human EC cells have been performed. We tested the susceptibility of human EC cells to transduction by retroviral vectors derived from three different retroviral genera...
October 26, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27601472/o-glcnacase-is-an-rna-polymerase-ii-elongation-factor-coupled-to-pausing-factors-spt5-and-tif1%C3%AE
#3
Melissa Resto, Bong-Hyun Kim, Alfonso G Fernandez, Brian J Abraham, Keji Zhao, Brian A Lewis
We describe here the identification and functional characterization of the enzyme O-GlcNAcase (OGA) as an RNA polymerase II elongation factor. Using in vitro transcription elongation assays, we show that OGA activity is required for elongation in a crude nuclear extract system, whereas in a purified system devoid of OGA the addition of rOGA inhibited elongation. Furthermore, OGA is physically associated with the known RNA polymerase II (pol II) pausing/elongation factors SPT5 and TRIM28-KAP1-TIF1β, and a purified OGA-SPT5-TIF1β complex has elongation properties...
October 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27364555/metabolic-stress-induced-phosphorylation-of-kap1-ser473-blocks-mitochondrial-fusion-in-breast-cancer-cells
#4
Chun-Ting Cheng, Ching-Ying Kuo, Ching Ouyang, Chien-Feng Li, Yiyin Chung, David C Chan, Hsing-Jien Kung, David K Ann
Mitochondrial dynamics during nutrient starvation of cancer cells likely exert profound effects on their capability for metastatic progression. Here, we report that KAP1 (TRIM28), a transcriptional coadaptor protein implicated in metastatic progression in breast cancer, is a pivotal regulator of mitochondrial fusion in glucose-starved cancer cells. Diverse metabolic stresses induced Ser473 phosphorylation of KAP1 (pS473-KAP1) in a ROS- and p38-dependent manner. Results from live-cell imaging and molecular studies revealed that during the first 6 to 8 hours of glucose starvation, mitochondria initially underwent extensive fusion, but then subsequently fragmented in a pS473-KAP1-dependent manner...
September 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27128603/7skiing-on-chromatin-move-globally-act-locally
#5
Iván D'Orso
RNA polymerase II (Pol II) pausing at promoter-proximal regions is a highly regulated step in the transcription cycle. Pause release is facilitated by the P-TEFb kinase, which phosphorylates Pol II and negative elongation factors. Recent studies suggest that P-TEFb (as part of the inhibitory 7SK snRNP) is recruited to promoter-proximal regions through interaction with KAP1/TRIM28/TIF1β to facilitate 'on-site' kinase activation and transcription elongation. Here, I discuss features of this model and future challenges to further hone our understanding of transcriptional regulation including Pol II pausing and pause release...
June 2, 2016: RNA Biology
https://www.readbyqxmd.com/read/26981421/genome-wide-analysis-of-kap1-the-7sk-snrnp-complex-and-rna-polymerase-ii
#6
Ryan P McNamara, Carlos Guzman, Jonathan E Reeder, Iván D'Orso
The transition of RNA polymerase II (Pol II) from transcription initiation into productive elongation in eukaryotic cells is regulated by the P-TEFb kinase, which phosphorylates the C-terminal domain of paused Pol II at promoter-proximal regions. Our recent study found that P-TEFb (in an inhibited state bound to the 7SK snRNP complex) interacts with the KAP1/TRIM28 transcriptional regulator, and that KAP1 and the 7SK snRNP co-occupy most gene promoters containing paused Pol II. Here we provide a detailed experimental description and analysis of the ChIP-seq datasets that have been deposited into Gene Expression Omnibus (GEO): GS72622, so that independent groups can replicate and expand upon these findings...
March 2016: Genomics Data
https://www.readbyqxmd.com/read/26055329/trim28-is-an-e3-ligase-for-arf-mediated-npm1-b23-sumoylation-that-represses-centrosome-amplification
#7
Shu Hui Neo, Yoko Itahana, Jennifer Alagu, Mayumi Kitagawa, Alvin Kunyao Guo, Sang Hyun Lee, Kai Tang, Koji Itahana
The tumor suppressor ARF enhances the SUMOylation of target proteins; however, the physiological function of ARF-mediated SUMOylation has been unclear due to the lack of a known, associated E3 SUMO ligase. Here we uncover TRIM28/KAP1 as a novel ARF-binding protein and SUMO E3 ligase for NPM1/B23. ARF and TRIM28 cooperate to SUMOylate NPM1, a nucleolar protein that regulates centrosome duplication and genomic stability. ARF-mediated SUMOylation of NPM1 was attenuated by TRIM28 depletion and enhanced by TRIM28 overexpression...
August 2015: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/25977998/different-atm-signaling-in-response-to-chromium-vi-metabolism-via-ascorbate-and-nonascorbate-reduction-implications-for-in-vitro-models-and-toxicogenomics
#8
Michal W Luczak, Samantha E Green, Anatoly Zhitkovich
BACKGROUND: Carcinogenic hexavalent chromium [Cr(VI)] requires cellular reduction to generate DNA damage. Metabolism of Cr(VI) by its principal reducer ascorbate (Asc) lacks a Cr(V) intermediate, which is abundant in reactions with a minor reducing agent, glutathione. Cultured cells are widely used in mechanistic studies of Cr(VI) toxicity; however, they typically contain < 1% of normal Asc levels. Asc deficiency is also expected to diminish protection against reactive oxygen species...
January 2016: Environmental Health Perspectives
https://www.readbyqxmd.com/read/25938714/histone-h3-3-is-required-for-endogenous-retroviral-element-silencing-in-embryonic-stem-cells
#9
Simon J Elsässer, Kyung-Min Noh, Nichole Diaz, C David Allis, Laura A Banaszynski
Transposable elements comprise roughly 40% of mammalian genomes. They have an active role in genetic variation, adaptation and evolution through the duplication or deletion of genes or their regulatory elements, and transposable elements themselves can act as alternative promoters for nearby genes, resulting in non-canonical regulation of transcription. However, transposable element activity can lead to detrimental genome instability, and hosts have evolved mechanisms to silence transposable element mobility appropriately...
June 11, 2015: Nature
https://www.readbyqxmd.com/read/25881176/dna-methylation-dynamics-at-imprinted-genes-during-bovine-pre-implantation-embryo-development
#10
Alan M O'Doherty, David A Magee, Lynee C O'Shea, Niamh Forde, Marijke E Beltman, Solomon Mamo, Trudee Fair
BACKGROUND: In mammals, maternal differentially methylated regions (DMRs) acquire DNA methylation during the postnatal growth stage of oogenesis, with paternal DMRs acquiring DNA methylation in the perinatal prospermatagonia. Following fusion of the male and female gametes, it is widely accepted that murine DNA methylation marks at the DMRs of imprinted genes are stable through embryogenesis and early development, until they are reprogrammed in primordial germ cells. However, the DNA methylation dynamics at DMRs of bovine imprinted genes during early stages of development remains largely unknown...
2015: BMC Developmental Biology
https://www.readbyqxmd.com/read/25846574/release-of-human-cytomegalovirus-from-latency-by-a-kap1-trim28-phosphorylation-switch
#11
Benjamin Rauwel, Suk Min Jang, Marco Cassano, Adamandia Kapopoulou, Isabelle Barde, Didier Trono
Human cytomegalovirus (HCMV) is a highly prevalent pathogen that induces life-long infections notably through the establishment of latency in hematopoietic stem cells (HSC). Bouts of reactivation are normally controlled by the immune system, but can be fatal in immuno-compromised individuals such as organ transplant recipients. Here, we reveal that HCMV latency in human CD34(+) HSC reflects the recruitment on the viral genome of KAP1, a master co-repressor, together with HP1 and the SETDB1 histone methyltransferase, which results in transcriptional silencing...
April 7, 2015: ELife
https://www.readbyqxmd.com/read/25421577/kap1-promotes-proliferation-and-metastatic-progression-of-breast-cancer-cells
#12
Joseph B Addison, Colton Koontz, James H Fugett, Chad J Creighton, Dongquan Chen, Mark K Farrugia, Renata R Padon, Maria A Voronkova, Sarah L McLaughlin, Ryan H Livengood, Chen-Chung Lin, J Michael Ruppert, Elena N Pugacheva, Alexey V Ivanov
KAP1 (TRIM28) is a transcriptional regulator in embryonic development that controls stem cell self-renewal, chromatin organization, and the DNA damage response, acting as an essential corepressor for KRAB family zinc finger proteins (KRAB-ZNF). To gain insight into the function of this large gene family, we developed an antibody that recognizes the conserved zinc fingers linker region (ZnFL) in multiple KRAB-ZNF. Here, we report that the expression of many KRAB-ZNF along with active SUMOlyated KAP1 is elevated widely in human breast cancers...
January 15, 2015: Cancer Research
https://www.readbyqxmd.com/read/25274305/an-evolutionary-arms-race-between-krab-zinc-finger-genes-znf91-93-and-sva-l1-retrotransposons
#13
Frank M J Jacobs, David Greenberg, Ngan Nguyen, Maximilian Haeussler, Adam D Ewing, Sol Katzman, Benedict Paten, Sofie R Salama, David Haussler
Throughout evolution primate genomes have been modified by waves of retrotransposon insertions. For each wave, the host eventually finds a way to repress retrotransposon transcription and prevent further insertions. In mouse embryonic stem cells, transcriptional silencing of retrotransposons requires KAP1 (also known as TRIM28) and its repressive complex, which can be recruited to target sites by KRAB zinc-finger (KZNF) proteins such as murine-specific ZFP809 which binds to integrated murine leukaemia virus DNA elements and recruits KAP1 to repress them...
December 11, 2014: Nature
https://www.readbyqxmd.com/read/25225599/kaptain-in-charge-of-multiple-missions-emerging-roles-of-kap1
#14
REVIEW
Chun-Ting Cheng, Ching-Ying Kuo, David K Ann
KAP1/TRIM28/TIF1β was identified nearly twenty years ago as a universal transcriptional co-repressor because it interacts with a large KRAB-containing zinc finger protein (KRAB-ZFP) transcription factor family. Many studies demonstrate that KAP1 affects gene expression by regulating the transcription of KRAB-ZFP-specific loci, trans-repressing as a transcriptional co-repressor or epigenetically modulating chromatin structure. Emerging evidence suggests that KAP1 also functions independent of gene regulation by serving as a SUMO/ubiquitin E3 ligase or signaling scaffold protein to mediate signal transduction...
August 26, 2014: World Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25160591/trim28-kap1-regulates-senescence
#15
Joana Santos, Jesús Gil
Senescence is a highly stable cell cycle arrest which limits the replication of cells with damaged genomes. The senescence program is activated during aging or in response to insults like DNA damage or oncogenic signaling. Upon induction of senescence, cells undergo profound changes on their transcription program, chromatin organization, and they secrete a complex mixture of mainly pro-inflammatory components termed the senescence-associated secretory phenotype (SASP). The SASP mediates multiple effects, including reinforcing senescence and activating immune surveillance responses...
November 2014: Immunology Letters
https://www.readbyqxmd.com/read/25092915/metastasis-associated-protein-ribosomal-rna-processing-1-homolog-b-rrp1b-modulates-metastasis-through-regulation-of-histone-methylation
#16
Minnkyong Lee, Amy M Dworkin, Jens Lichtenberg, Shashank J Patel, Niraj S Trivedi, Derek Gildea, David M Bodine, Nigel P S Crawford
UNLABELLED: Overexpression of ribosomal RNA processing 1 homolog B (RRP1B) induces a transcriptional profile that accurately predicts patient outcome in breast cancer. However, the mechanism by which RRP1B modulates transcription is unclear. Here, the chromatin-binding properties of RRP1B were examined to define how it regulates metastasis-associated transcription. To identify genome-wide RRP1B-binding sites, high-throughput ChIP-seq was performed in the human breast cancer cell line MDA-MB-231 and HeLa cells using antibodies against endogenous RRP1B...
December 2014: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/24991018/ectopic-dnmt3l-triggers-assembly-of-a-repressive-complex-for-retroviral-silencing-in-somatic-cells
#17
Tzu-Hao Kao, Hung-Fu Liao, Daniel Wolf, Kang-Yu Tai, Ching-Yu Chuang, Hsuan-Shu Lee, Hung-Chih Kuo, Kenichiro Hata, Xing Zhang, Xiaodong Cheng, Stephen P Goff, Steen K T Ooi, Timothy H Bestor, Shau-Ping Lin
UNLABELLED: Mammalian genomes are replete with retrotransposable elements, including endogenous retroviruses. DNA methyltransferase 3-like (DNMT3L) is an epigenetic regulator expressed in prospermatogonia, growing oocytes, and embryonic stem (ES) cells. Here, we demonstrate that DNMT3L enhances the interaction of repressive epigenetic modifiers, including histone deacetylase 1 (HDAC1), SET domain, bifurcated 1 (SETDB1), DNA methyltransferase 3A (DNMT3A), and tripartite motif-containing protein 28 (TRIM28; also known as TIF1β and KAP1) in ES cells and orchestrates retroviral silencing activity with TRIM28 through mechanisms including, but not limited to, de novo DNA methylation...
September 2014: Journal of Virology
https://www.readbyqxmd.com/read/24907272/an-arginine-rich-motif-of-ring-finger-protein-4-rnf4-oversees-the-recruitment-and-degradation-of-the-phosphorylated-and-sumoylated-kr%C3%A3-ppel-associated-box-domain-associated-protein-1-kap1-trim28-protein-during-genotoxic-stress
#18
Ching-Ying Kuo, Xu Li, Xiang-Qian Kong, Cheng Luo, Che-Chang Chang, Yiyin Chung, Hsiu-Ming Shih, Keqin Kathy Li, David K Ann
Krüppel-associated box domain-associated protein 1 (KAP1) is a universal transcriptional corepressor that undergoes multiple posttranslational modifications (PTMs), including SUMOylation and Ser-824 phosphorylation. However, the functional interplay of KAP1 PTMs in regulating KAP1 turnover during DNA damage response remains unclear. To decipher the role and cross-talk of multiple KAP1 PTMs, we show here that DNA double strand break-induced KAP1 Ser-824 phosphorylation promoted the recruitment of small ubiquitin-like modifier (SUMO)-targeted ubiquitin E3 ligase, ring finger protein 4 (RNF4), and subsequent RNF4-mediated, SUMO-dependent degradation...
July 25, 2014: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/24836891/stat3-activated-gm-csfr%C3%AE-translocates-to-the-nucleus-and-protects-cll-cells-from-apoptosis
#19
Ping Li, David Harris, Zhiming Liu, Uri Rozovski, Alessandra Ferrajoli, Yongtao Wang, Carlos Bueso-Ramos, Inbal Hazan-Halevy, Srdana Grgurevic, William Wierda, Jan Burger, Susan O'Brien, Stefan Faderl, Michael Keating, Zeev Estrov
UNLABELLED: Here, it was determined that chronic lymphocytic leukemia (CLL) cells express the α subunit, but not the β subunit, of the granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR/CSF2R). GM-CSFRα was detected on the surface, in the cytosol, and in the nucleus of CLL cells via confocal microscopy, cell fractionation, and GM-CSFRα antibody epitope mapping. Because STAT3 is frequently activated in CLL and the GM-CSFRα promoter harbors putative STAT3 consensus binding sites, MM1 cells were transfected with truncated forms of the GM-CSFRα promoter, then stimulated with IL6 to activate STAT3 and to identify STAT3-binding sites...
September 2014: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/23735015/distinct-roles-of-kap1-hp1-and-g9a-glp-in-silencing-of-the-two-cell-specific-retrotransposon-mervl-in-mouse-es-cells
#20
Irina A Maksakova, Peter J Thompson, Preeti Goyal, Steven Jm Jones, Prim B Singh, Mohammad M Karimi, Matthew C Lorincz
BACKGROUND: In mouse embryonic stem cells (mESCs), transcriptional silencing of numerous class I and II endogenous retroviruses (ERVs), including IAP, ETn and MMERVK10C, is dependent upon the H3K9 methyltransferase (KMTase) SETDB1/ESET and its binding partner KAP1/TRIM28. In contrast, the H3K9 KMTases G9a and GLP and HP1 proteins are dispensable for this process. Intriguingly, MERVL retroelements are actively transcribed exclusively in the two-cell (2C) embryo, but the molecular basis of silencing of these class III ERVs at later developmental stages has not been systematically addressed...
2013: Epigenetics & Chromatin
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