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https://www.readbyqxmd.com/read/29335245/cdk9-mediated-phosphorylation-controls-the-interaction-of-tip60-with-the-transcriptional-machinery
#1
Prisca Brauns-Schubert, Florian Schubert, Manuela Wissler, Martina Weiss, Lisa Schlicher, Simon Bessler, Mariam Safavi, Cornelius Miething, Christoph Borner, Tilman Brummer, Ulrich Maurer
The acetyltransferase TIP60 is regulated by phosphorylation, and we have previously shown that phosphorylation of TIP60 on S86 by GSK-3 promotes p53-mediated induction of the BCL-2 protein PUMA. TIP60 phosphorylation by GSK-3 requires a priming phosphorylation on S90, and here, we identify CDK9 as a TIP60S90 kinase. We demonstrate that a phosphorylation-deficient mutant, TIP60S90A, exhibits reduced interaction with chromatin, histone 3 and RNA Pol II, while its association with the TIP60 complex subunit EPC1 is not affected...
January 15, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29321817/enhanced-myc-association-with-the-nua4-histone-acetyltransferase-complex-mediated-by-the-adenovirus-e1a-n-terminal-domain-activates-a-subset-of-myc-target-genes-highly-expressed-in-cancer-cells
#2
Ling-Jun Zhao, Paul M Loewenstein, Maurice Green
The proto-oncogene MYC is a transcription factor over-expressed in many cancers and required for cell survival. Its function is regulated by histone acetyltransferase (HAT) complexes, such as the GCN5 complex and the NuA4/Tip60 complex. However, the roles of the HAT complexes during MYC function in cancer have not been well characterized. We recently showed that adenovirus E1A and its N-terminal 80 aa region, E1A 1-80, interact with the NuA4 complex, through the E1A TRRAP-targeting (ET) domain, and enhance MYC association with the NuA4 complex...
November 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29321313/tip60-complex-inhibits-hbv-transcription
#3
Hironori Nishitsuji, Saneyuki Ujino, Keisuke Harada, Kunitada Shimotohno
Hepatitis B virus (HBV) is a global major health problem with over one million deaths annually caused by chronic liver damage. Understanding host factors that modulate HBV replication may aid the development of anti-HBV therapies. Our recent genome-wide small interfering RNA screen using recombinant HBV demonstrated that TIP60 inhibited HBV infection. Here, we show that TIP60 complex contributes to anti-HBV defense. The TIP60 complex bound to the HBV promoter and suppressed HBV transcription driven by the precore/core promoter...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29286399/live-imaging-of-breast-epithelial-cell-migration-after-the-transient-depletion-of-tip60
#4
Yanzhou Zhang, Grace SuShin Chia, Cheng Yong Tham, Sudhakar Jha
The wound-healing assay is efficient and one of the most economical ways to study cell migration in vitro. Conventionally, images are taken at the beginning and end of an experiment using a phase-contrast microscope, and the migration abilities of cells are evaluated by the closure of wounds. However, cell movement is a dynamic phenomenon, and a conventional method does not allow for tracking single-cell movement. To improve current wound-healing assays, we use live-cell imaging techniques to monitor cell migration in real time...
December 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29236775/active-site-targeted-covalent-irreversible-inhibitors-of-usp7-impair-the-functions-of-foxp3-t-regulatory-cells-by-promoting-ubiquitination-of-tip60
#5
Feng Wang, Liqing Wang, Jian Wu, Ivan Sokirniy, Phuong Nguyen, Thomas Bregnard, Joseph Weinstock, Michael Mattern, Irina Bezsonova, Wayne W Hancock, Suresh Kumar
Accumulation of Foxp3+ T-regulatory (Treg) cells in the tumor microenvironment is associated with tumor immune evasion and poor patient outcome in the case of many solid tumors. Current therapeutic strategies for blocking Treg functions are not Treg-specific, and display only modest and transient efficacy. Recent studies revealed that ubiquitin-specific protease 7 (USP7) is essential for Treg functions by stabilizing expression of Tip60 and Foxp3, which together are central to the development and maintenance of the Treg cell lineage...
2017: PloS One
https://www.readbyqxmd.com/read/29216538/tip60-contributes-to-porcine-embryonic-development-by-regulating-dna-damage-response
#6
Jing Guo, Wenjun Zhou, Ying-Jie Niu, Kyung-Tae Shin, Young Tae Heo, Nam-Hyung Kim, Xiang-Shun Cui
The acetyltransferase TIP60 (also known as Kat5) is a member of the MYST family of histone acetyltransferases and was initially identified as a cellular protein. TIP60 acetylates histone and non-histone proteins and is involved in diverse biological processes, including apoptosis, cell cycle, and DNA damage responses. In this study, a specific inhibitor of TIP60 was used to detect the function of TIP60 in porcine parthenogenetic embryos. The results showed that TIP60 inhibition impaired porcine parthenogenetic embryonic development...
December 2, 2017: Theriogenology
https://www.readbyqxmd.com/read/29192674/landscape-of-the-regulatory-elements-for-lysine-2-hydroxyisobutyrylation-pathway
#7
He Huang, Zhouqing Luo, Shankang Qi, Jing Huang, Peng Xu, Xiuxuan Wang, Li Gao, Fangyi Li, Jian Wang, Wenhui Zhao, Wei Gu, Zhucheng Chen, Lunzhi Dai, Junbiao Dai, Yingming Zhao
Short-chain fatty acids and their corresponding acyl-CoAs sit at the crossroads of metabolic pathways and play important roles in diverse cellular processes. They are also precursors for protein post-translational lysine acylation modifications. A noteworthy example is the newly identified lysine 2-hydroxyisobutyrylation (Khib) that is derived from 2-hydroxyisobutyrate and 2-hydroxyisobutyryl-CoA. Histone Khib has been shown to be associated with active gene expression in spermatogenic cells. However, the key elements that regulate this post-translational lysine acylation pathway remain unknown...
December 1, 2017: Cell Research
https://www.readbyqxmd.com/read/29174981/acetylation-of-tip60-at-k104-is-essential-for-metabolic-stress-induced-apoptosis-in-cells-of-hepatocellular-cancer
#8
Xiao Fang, Guojun Lu, Kyungsoo Ha, Han Lin, Ye Du, Qiuhong Zuo, Yi Fu, Chaoxia Zou, Pumin Zhang
Tumor cells often encounter hypoglycemic microenvironment due to rapid cell expansion. It remains elusive how tumors reprogram the genome to survive the metabolic stress. The tumor suppressor TIP60 functions as the catalytic subunit of the human NuA4 histone acetyltransferase (HAT) multi-subunit complex and is involved in many different cellular processes including DNA damage response, cell growth and apoptosis. Attenuation of TIP60 expression has been detected in various tumor types. The function of TIP60 in tumor development has not been fully understood...
November 22, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29063469/effect-of-modified-wuzi-yanzong-pill-on-tip60-mediated-apoptosis-in-testis-of-male-rats-after-microwave-radiation
#9
Hai-Xiang Hu, Jing Sun, Ya-Jing Gao, Hong Fang, Shao-Qiang Xu, Jing Dong, Li-Zhao Wei, Shao-Bo Luo, Chuan-Yun Shen, Qi-Long Zhang, Ya-Lan Xie
OBJECTIVE: To investigate the effect of a modified Wuzi Yanzong Pill (, WZYZP) on the male rats' testis after microwave radiation, as well as its potential mechanism. METHODS: Forty-five male rats were randomly assigned to three groups: the control group, the radiation group, and the WZYZP group. The rats in the radiation group and WZYZP group were exposed to microwave radiation for 15 min once, while the rats in the control group were not exposed to any radiation...
October 24, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/29045464/tip60-represses-telomerase-expression-by-inhibiting-sp1-binding-to-the-tert-promoter
#10
Deepa Rajagopalan, Amit Kumar Pandey, Magdalene Claire Xiuzhen, Kwok Kin Lee, Shainan Hora, Yanzhou Zhang, Boon Haow Chua, Hui Si Kwok, Shreshtha Sailesh Bhatia, Lih Wen Deng, Daniel G Tenen, Dennis Kappei, Sudhakar Jha
HIV1-TAT interactive protein (TIP60) is a haploinsufficient tumor suppressor. However, the potential mechanisms endowing its tumor suppressor ability remain incompletely understood. It plays a vital role in virus-induced cancers where TIP60 down-regulates the expression of human papillomavirus (HPV) oncoprotein E6 which in turn destabilizes TIP60. This intrigued us to identify the role of TIP60, in the context of a viral infection, where it is targeted by oncoproteins. Through an array of molecular biology techniques such as Chromatin immunoprecipitation, expression analysis and mass spectrometry, we establish the hitherto unknown role of TIP60 in repressing the expression of the catalytic subunit of the human telomerase complex, TERT, a key driver for immortalization...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29040603/mitosis-specific-acetylation-tunes-ran-effector-binding-for-chromosome-segregation
#11
Xiaoling Bao, Heng Liu, Xing Liu, Ke Ruan, Yonghui Zhang, Zhiyong Zhang, Qi Hu, Ying Liu, Saima Akram, Jiahai Zhang, Qingguo Gong, Wenwen Wang, Xiao Yuan, Jian Li, Lingli Zhao, Zhen Dou, Ruijun Tian, Xuebiao Yao, Jihui Wu, Yunyu Shi
Stable transmission of genetic information during cell division requires faithful mitotic spindle assembly and chromosome segregation. The Ran GTPase plays a key role in mitotic spindle assembly. However, how the generation of a chemical gradient of Ran-GTP at the spindle is coupled to mitotic post-translational modifications has never been characterized. Here, we solved the complex structure of Ran with the nucleotide release factor Mog1 and delineated a novel mitosis-specific acetylation-regulated Ran-Mog1 interaction during chromosome segregation...
October 6, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29018219/spatially-restricted-loading-of-brd2-at-dna-double-strand-breaks-protects-h4-acetylation-domains-and-promotes-dna-repair
#12
Ozge Gursoy-Yuzugullu, Chelsea Carman, Brendan D Price
The n-terminal tail of histone H4 recruits repair proteins, including 53BP1, to DNA double-strand breaks (DSB) and undergoes dynamic acetylation during DSB repair. However, how H4 acetylation (H4Ac) recruits repair proteins and reorganizes chromatin during DNA repair is unclear. Here, we show that the bromodomain protein BRD2 is recruited to DSBs. This recruitment requires binding of BRD2's tandem bromodomains to H4Ac, which is generated at DSBs by the Tip60/KAT5 acetyltransferase. Binding of BRD2 to H4Ac protects the underlying acetylated chromatin from attack by histone deacetylases and allows acetylation to spread along the flanking chromatin...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28977657/h2ax-facilitates-classical-non-homologous-end-joining-at-the-expense-of-limited-nucleotide-loss-at-repair-junctions
#13
Yi-Li Feng, Ji-Feng Xiang, Si-Cheng Liu, Tao Guo, Guo-Fang Yan, Ye Feng, Na Kong, Hao-Dan Li, Yang Huang, Hui Lin, Xiu-Jun Cai, An-Yong Xie
Phosphorylated histone H2AX, termed 'γH2AX', mediates the chromatin response to DNA double strand breaks (DSBs) in mammalian cells. H2AX deficiency increases the numbers of unrepaired DSBs and translocations, which are partly associated with defects in non-homologous end joining (NHEJ) and contributing to genomic instability in cancer. However, the role of γH2AX in NHEJ of general DSBs has yet to be clearly defined. Here, we showed that despite little effect on overall NHEJ efficiency, H2AX deficiency causes a surprising bias towards accurate NHEJ and shorter deletions in NHEJ products...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28894190/novel-detection-of-post-translational-modifications-in-human-monocyte-derived-dendritic-cells-after-chronic-alcohol-exposure-role-of-inflammation-regulator-h4k12ac
#14
Tiyash Parira, Gloria Figueroa, Alejandra Laverde, Gianna Casteleiro, Mario E Gomez Hernandez, Francisco Fernandez-Lima, Marisela Agudelo
Previous reports on epigenetic mechanisms involved in alcohol abuse have focus on hepatic and neuronal regions, leaving the immune system and specifically monocyte-derived dendritic cells (MDDCs) understudied. Our lab has previously shown histone deacetylases are modulated in cells derived from alcohol users and after in vitro acute alcohol treatment of human MDDCs. In the current study, we developed a novel screening tool using matrix assisted laser desorption ionization-fourier transform-ion cyclotron resonance mass spectrometry (MALDI-FT-ICR MS) and single cell imaging flow cytometry to detect post-translational modifications (PTMs) in human MDDCs due to chronic alcohol exposure...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28884217/critical-genomic-regulation-mediated-by-enhancer-of-polycomb
#15
REVIEW
Naomi E Searle, Lorraine Pillus
Enhancer of Polycomb (EPC) was first identified for its contributions to development in Drosophila and was soon-thereafter purified as a subunit of the NuA4/TIP60 acetyltransferase complex. Since then, EPC has often been left in the shadows as an essential, yet non-catalytic subunit of NuA4/TIP60; however, its deep conservation and disease association make clear that it warrants additional attention. In fact, recent studies in yeast demonstrated that its Enhancer of Polycomb, Epl1, was just as important for gene expression and acetylation as is the catalytic subunit of NuA4...
September 7, 2017: Current Genetics
https://www.readbyqxmd.com/read/28884116/the-role-of-pontin-and-reptin-in-cellular-physiology-and-cancer-etiology
#16
REVIEW
Yu-Qian Mao, Walid A Houry
Pontin (RUVBL1, TIP49, TIP49a, Rvb1) and Reptin (RUVBL2, TIP48, TIP49b, Rvb2) are highly conserved ATPases of the AAA+ (ATPases Associated with various cellular Activities) superfamily and are involved in various cellular processes that are important for oncogenesis. First identified as being upregulated in hepatocellular carcinoma and colorectal cancer, their overexpression has since been shown in multiple cancer types such as breast, lung, gastric, esophageal, pancreatic, kidney, bladder as well as lymphatic, and leukemic cancers...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28873018/tip60-histone-acetyltransferase-in-adipose-tissue-possible-linkages-with-breast-cancer-development
#17
Gaëlle Judes, Lucas Dubois, Khaldoun Rifaï, Marine Daures, Mouhamed Idrissou, Yves-Jean Bignon, Frédérique Penault-Llorca, Dominique Bernard-Gallon
No abstract text is available yet for this article.
November 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28871603/targeting-histone-acetyltransferase-tip60-inhibits-intestinal-allergy
#18
Gui Yang, Bao-Hui Cheng, Shao-Bo Yang, Zhi-Qiang Liu, Shu-Qi Qiu, Li-Tao Yang, Rui-Di Xie, Xiao-Rui Geng, Mao-Gang Li, Lin Gao, Zhi-Gang Liu, Ping-Chang Yang
BACKGROUND: The over production of IgE plays a critical role in the pathogenesis of allergy; the mechanism is unclear. Histone acetyltransferase (HAT) activities are required in gene transcription of a large number of molecules in the immune system of the body. OBJECTIVES: This study tests a hypothesis that HAT Tat-interactive protein 60 (Tip60) plays an important role in the initiation of IgE-mediated allergy. METHODS: The effects of Tip60 on regulating IgE expression were assessed with B cells...
September 4, 2017: Allergy
https://www.readbyqxmd.com/read/28837777/arsenite-binds-to-the-zinc-finger-motif-of-tip60-histone-acetyltransferase-and-induces-its-degradation-via-the-26s-proteasome
#19
Lok Ming Tam, Ji Jiang, Pengcheng Wang, Lin Li, Weili Miao, Xuejiao Dong, Yinsheng Wang
Arsenic is a ubiquitous environmental contaminant with widespread public health concern. Epidemiological studies have revealed that chronic human exposure to arsenic in drinking water is associated with the prevalence of skin, lung, and bladder cancers. Aberrant histone modifications (e.g., methylation, acetylation, and ubiquitination) were previously found to be accompanied by arsenic exposure; thus, perturbation of epigenetic pathways is thought to contribute to arsenic carcinogenesis. Arsenite is known to interact with zinc finger motifs of proteins, and zinc finger motif is present in and indispensable for the enzymatic activities of crucial histone-modifying enzymes especially the MYST family of histone acetyltransferases (e...
September 18, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28819431/tat-interactive-protein-60kda-tip60-regulates-the-tumorigenesis-of-lung-cancer-in-vitro
#20
Yang Yang, Jian Sun, Ting Chen, Zengyue Tao, Xianwei Zhang, Feng Tian, Xiao Zhou, Daru Lu
Histone acetyltransferases (HATs) play vital functions in the tumorigenesis of many solid organ malignancies. We previously screened a human HATs cDNA library and identified Tat-interactive protein-60KDa (TIP60) as a candidate critical HATs in the origination of lung cancer. In this study, our data suggested that overexpression of TIP60 inhibited the cell viability of A549 and H1299 cells since day 2. Compared to the control group, the viability of these two lung cancer cells was inhibited by 25% and 19% at day 6 with the overexpression of TIP60...
2017: Journal of Cancer
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