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https://www.readbyqxmd.com/read/27910233/a-genetically-encoded-allysine-for-the-synthesis-of-proteins-with-site-specific-lysine-dimethylation
#1
Zhipeng A Wang, Yu Zeng, Yadagiri Kurra, Xin Wang, Jeffery M Tharp, Erol C Vatansever, Willie W Hsu, Susie Dai, Xinqiang Fang, Wenshe R Liu
Using the amber suppression approach, N(ϵ) -(4-azidobenzoxycarbonyl)-δ,ϵ-dehydrolysine, an allysine precursor is genetically encoded in E. coli. Its genetic incorporation followed by two sequential biocompatible reactions allows convenient synthesis of proteins with site-specific lysine dimethylation. Using this approach, dimethyl-histone H3 and p53 proteins have been synthesized and used to probe functions of epigenetic enzymes including histone demethylase LSD1 and histone acetyltransferase Tip60. We confirmed that LSD1 is catalytically active toward H3K4me2 and H3K9me2 but inert toward H3K36me2, and methylation at p53 K372 directly activates Tip60 for its catalyzed acetylation at p53 K120...
December 2, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27899423/myc-mediates-mrna-cap-methylation-of-canonical-wnt-beta-catenin-signaling-transcripts-by-recruiting-cdk7-and-rna-methyltransferase
#2
Valeriya Posternak, Matthew H Ung, Chao Cheng, Michael D Cole
: MYC is a pleiotropic transcription factor that activates and represses a wide range of target genes and is frequently deregulated in human tumors. While much is known about the role of MYC in transcriptional activation and repression, MYC can also regulate mRNA cap methylation through a mechanism that has remained poorly understood. Here it is reported that MYC enhances mRNA cap methylation of transcripts globally, specifically increasing mRNA cap methylation of genes involved in Wnt/beta-catenin signaling...
November 29, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27814680/ataxia-telangiectasia-mutated-atm-interacts-with-p400-atpase-for-an-efficient-dna-damage-response
#3
Rebecca J Smith, Matthew S Savoian, Lauren E Weber, Jeong Hyeon Park
BACKGROUND: Ataxia telangiectasia mutated (ATM) and TRRAP proteins belong to the phosphatidylinositol 3-kinase-related kinase family and are involved in DNA damage repair and chromatin remodeling. ATM is a checkpoint kinase that is recruited to sites of DNA double-strand breaks where it phosphorylates a diverse range of proteins that are part of the chromatin and DNA repair machinery. As an integral subunit of the TRRAP-TIP60 complexes, p400 ATPase is a chromatin remodeler that is also targeted to DNA double-strand break sites...
November 4, 2016: BMC Molecular Biology
https://www.readbyqxmd.com/read/27798113/oral-facial-digital-syndrome-type-i-cells-exhibit-impaired-dna-repair-unanticipated-consequences-of-defective-ofd1-outside-of-the-cilia-network
#4
Iga Abramowicz, Gillian Carpenter, Mariaevelina Alfieri, Rita Colnaghi, Emily Outwin, Philippe Parent, Christel Thauvin-Robinet, Daniela Iaconis, Brunella Franco, Mark O'Driscoll
Defects in OFD1 underlie the clinically complex ciliopathy, Oral-Facial-Digital syndrome Type I (OFD Type I). Our understanding of the molecular, cellular and clinical consequences of impaired OFD1 originate from its characterised roles at the centrosome/basal body/cilia network. Nonetheless, the first described OFD1 interactors were components of the TIP60 histone acetyltransferase complex. We find that OFD1 can also localise to chromatin and its reduced expression is associated with mis-localization of TIP60 in patient-derived cell lines...
October 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27777629/an-h4k16-histone-acetyltransferase-mediates-decondensation-of-the-x-chromosome-in-c-elegans-males
#5
Alyssa C Lau, Kevin P Zhu, Elizabeth A Brouhard, Michael B Davis, Györgyi Csankovszki
BACKGROUND: In C. elegans, in order to equalize gene expression between the sexes and balance X and autosomal expression, two steps are believed to be required. First, an unknown mechanism is hypothesized to upregulate the X chromosome in both sexes. This mechanism balances the X to autosomal expression in males, but creates X overexpression in hermaphrodites. Therefore, to restore the balance, hermaphrodites downregulate gene expression twofold on both X chromosomes. While many studies have focused on X chromosome downregulation, the mechanism of X upregulation is not known...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27769803/ubiquitin-specific-protease-7-inhibition-impairs-tip60-dependent-foxp3-t-regulatory-cell-function-and-promotes-antitumor-immunity
#6
Liqing Wang, Suresh Kumar, Satinder Dahiya, Feng Wang, Jian Wu, Kheng Newick, Rongxiang Han, Arabinda Samanta, Ulf H Beier, Tatiana Akimova, Tricia R Bhatti, Benjamin Nicholson, Mathew P Kodrasov, Saket Agarwal, David E Sterner, Wei Gu, Joseph Weinstock, Tauseef R Butt, Steven M Albelda, Wayne W Hancock
Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3...
October 15, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27768769/depletion-of-tip60-from-in-vivo-cardiomyocytes-increases-myocyte-density-followed-by-cardiac-dysfunction-myocyte-fallout-and-lethality
#7
Joseph B Fisher, Audrey Horst, Tina Wan, Min-Su Kim, John Auchampach, John Lough
Tat-interactive protein 60 (Tip60), encoded by the Kat5 gene, is a member of the MYST family of acetyltransferases. Cancer biology studies have shown that Tip60 induces the DNA damage response, apoptosis, and cell-cycle inhibition. Although Tip60 is expressed in the myocardium, its role in cardiomyocytes (CMs) is unclear. Earlier studies here showed that application of cardiac stress to globally targeted Kat5+/-haploinsufficient mice resulted in inhibition of apoptosis and activation of the CM cell-cycle, despite only modest reduction of Tip60 protein levels...
2016: PloS One
https://www.readbyqxmd.com/read/27743347/e3-ligase-uhrf2-stabilizes-the-acetyltransferase-tip60-and-regulates-h3k9ac-and-h3k14ac-via-ring-finger-domain
#8
Shengyuan Zeng, Yangyang Wang, Ting Zhang, Lu Bai, Yalan Wang, Changzhu Duan
UHRF2 is a ubiquitin-protein ligase E3 that regulates cell cycle, genomic stability and epigenetics. We conducted a co-immunoprecipitation assay and found that TIP60 and HDAC1 interact with UHRF2. We previously demonstrated that UHRF2 regulated H3K9ac and H3K14ac differentially in normal and cancer cells. However, the accurate signal transduction mechanisms were not clear. In this study, we found that TIP60 acted downstream of UHRF2 to regulate H3K9ac and H3K14ac expression. TIP60 is stabilized in normal cells by UHRF2 ubiquitination...
October 14, 2016: Protein & Cell
https://www.readbyqxmd.com/read/27688101/the-effect-of-human-papillomavirus-on-dna-repair-in-head-and-neck-squamous-cell-carcinoma
#9
REVIEW
Garren M Low, David S Thylur, Vicky N Yamamoto, Uttam K Sinha
Much of the current literature regarding the molecular pathophysiology of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has focused on the virus's effect on cell cycle modulation and cell proliferation. A second mechanism of pathogenicity employed by HPV, dysregulation of cellular DNA repair processes, has been more sparsely studied. The purpose of this review is to describe current understanding about the effect of HPV on DNA repair in HNSCC, taking cues from cervical cancer literature...
October 2016: Oral Oncology
https://www.readbyqxmd.com/read/27678523/x-chromosome-crossover-formation-and-genome-stability-in-caenorhabditis-elegans-are-independently-regulated-by-xnd-1
#10
T Brooke McClendon, Rana Mainpal, Francis Raj Gandhi Amrit, Michael W Krause, Arjumand Ghazi, Judith L Yanowitz
The germ line efficiently combats numerous genotoxic insults to ensure the high fidelity propagation of unaltered genomic information across generations. Yet, germ cells in most metazoans also intentionally create double-strand breaks (DSBs) to promote DNA exchange between parental chromosomes, a process known as crossing over. Homologous recombination is employed in the repair of both genotoxic lesions and programmed DSBs and many of the core DNA repair proteins function in both processes. In addition, DNA repair efficiency and crossover distribution are both influenced by local and global differences in chromatin structure, yet the interplay between chromatin structure, genome integrity, and meiotic fidelity is still poorly understand...
October 5, 2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27670582/tip60-main-functions-and-its-inhibitors
#11
Xiaoli Zhang, Jiyong Wu, Yepeng Luan
Tip60, the founding member of MYST histone acetyltransferase family, was originally identified as a cellular acetyltransferase protein that interacts with HIV-1 Tat. Tip60 plays roles in many processes such as cellular signaling transmission, DNA damage repair, cell cycle and checkpoint control and apoptosis by acetylating its histone or non-histone substrates. Dysfunction of Tip60 could promote or suppress diseases including different kinds of cancers. Here, some main functions and its known inhibitors were summarized...
September 23, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27664947/ad-e1a-243r-oncoprotein-promotes-association-of-proto-oncogene-product-myc-with-the-nua4-tip60-complex-via-the-e1a-n-terminal-repression-domain
#12
Ling-Jun Zhao, Paul M Loewenstein, Maurice Green
The adenovirus E1A 243R oncoprotein targets TRRAP, a scaffold protein that assembles histone acetyltransferase (HAT) complexes, such as the NuA4/Tip60 complex which mediates transcriptional activity of the proto-oncogene MYC and helps determine the cancer cell phenotype. How E1A transforms cells through TRRAP remains obscure. We performed proteomic analysis with the N-terminal transcriptional repression domain of E1A 243R (E1A 1-80) and showed that E1A 1-80 interacts with TRRAP, p400, and three other members of the NuA4 complex - DMAP1, RUVBL1 and RUVBL2 - not previously shown to associate with E1A 243R...
December 2016: Virology
https://www.readbyqxmd.com/read/27651430/tip60-inhibits-metastasis-by-ablating-dnmt1-snail2-driven-epithelial-mesenchymal-transition-program
#13
Yanzhou Zhang, Vanitha Krishna Subbaiah, Deepa Rajagopalan, Cheng Yong Tham, Lissa Nurrul Abdullah, Tan Boon Toh, Min Gong, Tuan Zea Tan, Shweta Pradip Jadhav, Amit Kumar Pandey, Neerja Karnani, Edward Kai-Hua Chow, Jean Paul Thiery, Sudhakar Jha
HIV-Tat-interacting protein of 60 kDa (TIP60) is a lysine acetyltransferase and known to be downregulated in multiple cancers. Among various signalling pathways, TIP60 is implicated in regulating epithelial-mesenchymal transition (EMT). Here, we show that TIP60 expression abrogates cell migration and metastatic potential of breast cancer cells using in vitro and in vivo models. Mechanistically, we show that this is through its ability to destabilize DNMT1 and inhibit SNAIL2 function (SNAIL2-mediated EMT/cell migration)...
September 20, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27644079/extensive-nuclear-sphere-generation-in-the-human-alzheimer-s-brain
#14
Katharina Kolbe, Hassan Bukhari, Christina Loosse, Gregor Leonhardt, Annika Glotzbach, Magdalena Pawlas, Katharina Hess, Carsten Theiss, Thorsten Müller
Nuclear spheres are protein aggregates consisting of FE65, TIP60, BLM, and other yet unknown proteins. Generation of these structures in the cellular nucleus is putatively modulated by the amyloid precursor protein (APP), either by its cleavage or its phosphorylation. Nuclear spheres were preferentially studied in cell culture models and their existence in the human brain had not been known. Existence of nuclear spheres in the human brain was studied using immunohistochemistry. Cell culture experiments were used to study regulative mechanisms of nuclear sphere generation...
August 26, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27623778/the-silent-information-regulator-1-sirt1-is-a-positive-regulator-of-the-notch-pathway-in-drosophila
#15
Matej Horvath, Zorana Mihajlovic, Vera Slaninova, Raquel Perez Gomez, Yuri Moshkin, Alena Krejci
The silent information regulator 1 (Sirt1) has previously been shown to have negative effects on the Notch pathway in several contexts. We bring evidence that Sirt1 has a positive effect on Notch activation in Drosophila, in the context of sensory organ precursor specification and during wing development. The phenotype of Sirt1 mutant resembles weak Notch loss of function phenotypes and genetic interactions of Sirt1 with the components of the Notch pathway also suggest a positive role of Sirt1 in Notch signalling...
September 13, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27528742/targeting-cancer-using-kat-inhibitors-to-mimic-lethal-knockouts
#16
REVIEW
James A L Brown, Emer Bourke, Leif A Eriksson, Michael J Kerin
Two opposing enzyme classes regulate fundamental elements of genome maintenance, gene regulation and metabolism, either through addition of an acetyl moiety by histone acetyltransferases (HATs) or its removal by histone de-acetyltransferases (HDAC), and are exciting targets for drug development. Importantly, dysfunctional acetylation has been implicated in numerous diseases, including cancer. Within the HAT superfamily the MYST family holds particular interest, as its members are directly involved in the DNA damage response and repair pathways and crucially, several members have been shown to be down-regulated in common cancers (such as breast and prostate)...
August 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27524627/notch1-inhibits-activation-of-atm-by-impairing-the-formation-of-an-atm-foxo3a-kat5-tip60-complex
#17
Marek Adamowicz, Jelena Vermezovic, Fabrizio d'Adda di Fagagna
The DNA damage response (DDR) signal transduction pathway is responsible for sensing DNA damage and further relaying this signal into the cell. ATM is an apical DDR kinase that orchestrates the activation and the recruitment of downstream DDR factors to induce cell-cycle arrest and repair. We have previously shown that NOTCH1 inhibits ATM activation upon DNA damage, but the underlying mechanism remains unclear. Here, we show that NOTCH1 does not impair ATM recruitment to DNA double-strand breaks (DSBs). Rather, NOTCH1 prevents binding of FOXO3a and KAT5/Tip60 to ATM through a mechanism in which NOTCH1 competes with FOXO3a for ATM binding...
August 23, 2016: Cell Reports
https://www.readbyqxmd.com/read/27461052/novel-synthetic-lethality-screening-method-identifies-tip60-dependent-radiation-sensitivity-in-the-absence-of-baf180
#18
Suzanna R Hopkins, Grant A McGregor, Johanne M Murray, Jessica A Downs, Velibor Savic
In recent years, research into synthetic lethality and how it can be exploited in cancer treatments has emerged as major focus in cancer research. However, the lack of a simple to use, sensitive and standardised assay to test for synthetic interactions has been slowing the efforts. Here we present a novel approach to synthetic lethality screening based on co-culturing two syngeneic cell lines containing individual fluorescent tags. By associating shRNAs for a target gene or control to individual fluorescence labels, we can easily follow individual cell fates upon siRNA treatment and high content imaging...
October 2016: DNA Repair
https://www.readbyqxmd.com/read/27454757/tip60-hat-action-mediates-environmental-enrichment-induced-cognitive-restoration
#19
Songjun Xu, Priyalakshmi Panikker, Sahira Iqbal, Felice Elefant
Environmental enrichment (EE) conditions have beneficial effects for reinstating cognitive ability in neuropathological disorders like Alzheimer's disease (AD). While EE benefits involve epigenetic gene control mechanisms that comprise histone acetylation, the histone acetyltransferases (HATs) involved remain largely unknown. Here, we examine a role for Tip60 HAT action in mediating activity- dependent beneficial neuroadaptations to EE using the Drosophila CNS mushroom body (MB) as a well-characterized cognition model...
2016: PloS One
https://www.readbyqxmd.com/read/27320910/the-tip60-complex-is-a-conserved-coactivator-of-hif1a
#20
Joel I Perez-Perri, Veronica L Dengler, K Audrey Audetat, Ahwan Pandey, Elizabeth A Bonner, Marjeta Urh, Jacqui Mendez, Danette L Daniels, Pablo Wappner, Matthew D Galbraith, Joaquín M Espinosa
Hypoxia-inducible factors (HIFs) are critical regulators of the cellular response to hypoxia. Despite their established roles in normal physiology and numerous pathologies, the molecular mechanisms by which they control gene expression remain poorly understood. We report here a conserved role for the TIP60 complex as a HIF1 transcriptional cofactor in Drosophila and human cells. TIP60 (KAT5) is required for HIF1-dependent gene expression in fly cells and embryos and colorectal cancer cells. HIF1A interacts with and recruits TIP60 to chromatin...
June 28, 2016: Cell Reports
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