Short Article
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Functional Roles of Bromodomain Proteins in Cancer
cancers Review Functional Roles of Bromodomain Proteins in Cancer Samuel P. Boyson 1,2, Cong Gao 3, Kathleen Quinn 2,3, Joseph Boyd 3, Hana Paculova 3 , Seth Frietze 3,4,* and Karen C. Glass 1,2,4,* 1 Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT 05446, USA; [email protected] 2 Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA; [email protected] 3 Department of Biomedical and Health Sciences, University of Vermont, Burlington, VT 05405, USA; [email protected] (C.G.); [email protected] (J.B.); [email protected] (H.P.) 4 University of Vermont Cancer Center, Burlington, VT 05405, USA * Correspondence: [email protected] (S.F.); [email protected] (K.C.G.) Simple Summary: This review provides an in depth analysis of the role of bromodomain-containing proteins in cancer development. As readers of acetylated lysine on nucleosomal histones, bromod- omain proteins are poised to activate gene expression, and often promote cancer progression. We examined changes in gene expression patterns that are observed in bromodomain-containing proteins and associated with specific cancer types. We also mapped the protein–protein interaction network for the human bromodomain-containing proteins, discuss the cellular roles of these epigenetic regu- lators as part of nine different functional groups, and identify bromodomain-specific mechanisms in cancer development. Lastly, we summarize emerging strategies to target bromodomain proteins in cancer therapy, including those that may be essential for overcoming resistance. Overall, this review provides a timely discussion of the different mechanisms of bromodomain-containing pro- Citation: Boyson, S.P.; Gao, C.; teins in cancer, and an updated assessment of their utility as a therapeutic target for a variety of Quinn, K.; Boyd, J.; Paculova, H.; cancer subtypes. -
Chip Validated H4k5ac (Clone RM140) Antibody with Positive and Negative Primer Sets
www.chromatrap.com Clywedog Rd South Wrexham Industrial Estate Wrexham LL13 9XS, United Kingdom Tel: +44 (0) 1978 666239/40 Email: [email protected] ChIP Validated H4K5ac (Clone RM140) Antibody with Positive and Negative Primer Sets Catalogue no: 900029 Chromatrap®’s ChIP Validated H4K5ac Antibody with Positive Primer Set provides a complete set of tools to assist with a successful ChIP assay. Including: H4K5ac antibody, control rabbit IgG, and positive primer set. The ChIP Validated H4K5ac Antibody with Positive Primer Set is not suitable for use with non-human species. Background: Histone 4 (H4) is one of the five core histone proteins, comprising the protein component of chromatin. H4 is ubiquitous within chromosomes and can be found bound to most gene sequences throughout the genome. Acetylation of lysine 5 on histone 4 (H4K5ac) is associated with open chromatin and active gene transcription. H4K5ac has been shown to have roles in epigenetic bookmarking, a process where genetic information is passed onto daughter cells during cell division. A rabbit IgG is included in this Antibody Primer Set as a negative control for the ChIP experiment. The H4K5ac positive primer set recognises the promoter of the GAPDH gene, associated with active transcription and is a suitable target for this antibody. Suggested Usage: Component Suggested Dilution Figure H4K5ac 2:1 (antibody: chromatin) 1 Rabbit IgG 2:1 (antibody: chromatin) 1 Positive Primer Set Dilute from 4M (provided) to 1M working concentration Please note: Optimal dilutions should be determined by the user. These volumes are stated as guidelines only. Advancements in Epigenetics *This product is for research use only. -
Trim33 Is Essential for Macrophage and Neutrophil Mobilization To
© 2017. Published by The Company of Biologists Ltd | Journal of Cell Science (2017) 130, 2797-2807 doi:10.1242/jcs.203471 RESEARCH ARTICLE Trim33 is essential for macrophage and neutrophil mobilization to developmental or inflammatory cues Doris Lou Demy1,2,*, Muriel Tauzin1,2,‡, Mylenè Lancino1,2,Véronique Le Cabec3,4, Michael Redd5, Emi Murayama1,2, Isabelle Maridonneau-Parini3,4, Nikolaus Trede5 and Philippe Herbomel1,2,§ ABSTRACT first organs to become colonized in this way in mammalian and Macrophages infiltrate and establish in developing organs from an avian embryogenesis is the central nervous system (CNS) (Sorokin early stage, often before these have become vascularized. Similarly, et al., 1992; Cuadros et al., 1993), and at least in mammals, the leukocytes, in general, can quickly migrate through tissues to any site resulting resident macrophages then comprise the microglia for the of wounding. This unique capacity is rooted in their characteristic whole life of the animal (Kierdorf et al., 2015). The molecular and amoeboid motility, the genetic basis of which is poorly understood. cellular determinants of this early colonization are mostly unknown. Trim33 (also known as Tif1-γ), a nuclear protein that associates In the zebrafish embryo, primitive macrophages born in the yolk sac with specific DNA-binding transcription factors to modulate gene colonize the tissues of the embryo, notably the head, brain and expression, has been found to be mainly involved in hematopoiesis retina, in a pattern very similar to that seen in mammalian and avian and gene regulation mediated by TGF-β. Here, we have discovered embryos (Herbomel et al., 2001). The M-CSF/CSF-1 receptor that in Trim33-deficient zebrafish embryos, primitive macrophages are (CSF1-R) was found to be dispensable for the differentiation of unable to colonize the central nervous system to become microglia. -
Transcriptomic and Proteomic Profiling Provides Insight Into
BASIC RESEARCH www.jasn.org Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy † † ‡ Peidi Liu,* Emelie Lassén,* Viji Nair, Celine C. Berthier, Miyuki Suguro, Carina Sihlbom,§ † | † Matthias Kretzler, Christer Betsholtz, ¶ Börje Haraldsson,* Wenjun Ju, Kerstin Ebefors,* and Jenny Nyström* *Department of Physiology, Institute of Neuroscience and Physiology, §Proteomics Core Facility at University of Gothenburg, University of Gothenburg, Gothenburg, Sweden; †Division of Nephrology, Department of Internal Medicine and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan; ‡Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan; |Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; and ¶Integrated Cardio Metabolic Centre, Karolinska Institutet Novum, Huddinge, Sweden ABSTRACT IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22). Using curated glomerular cell type–specific genes from the published literature, we found differential expression of a much higher percentage of mesangial cell–positive standard genes than podocyte-positive standard genes in IgAN. Principal coordinate analysis of expression data revealed clear separation of patient and control samples on the basis of mesangial but not podocyte cell–positive standard genes. -
Loss of TRIM33 Causes Resistance to BET Bromodomain Inhibitors Through MYC- and TGF-Β–Dependent Mechanisms
Loss of TRIM33 causes resistance to BET PNAS PLUS bromodomain inhibitors through MYC- and TGF-β–dependent mechanisms Xiarong Shia, Valia T. Mihaylovaa, Leena Kuruvillaa, Fang Chena, Stephen Vivianoa, Massimiliano Baldassarrea, David Sperandiob, Ruben Martinezb, Peng Yueb, Jamie G. Batesb, David G. Breckenridgeb, Joseph Schlessingera,1, Benjamin E. Turka,1, and David A. Calderwooda,c,1 aDepartment of Pharmacology, Yale University School of Medicine, New Haven, CT 06520; bGilead Sciences, Foster City, CA 94404; and cDepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06520 Contributed by Joseph Schlessinger, May 24, 2016 (sent for review December 22, 2015; reviewed by Gary L. Johnson and Michael B. Yaffe) Bromodomain and extraterminal domain protein inhibitors (BETi) not characterized by genetic alterations in BET proteins. One key hold great promise as a novel class of cancer therapeutics. Because mechanism by which BETi suppress growth and survival of at least acquired resistance typically limits durable responses to targeted some types of cancer cells is by preferentially repressing tran- therapies, it is important to understand mechanisms by which scription of the proto-oncogene MYC, which is often under the tumor cells adapt to BETi. Here, through pooled shRNA screening control of BRD4 (5, 10, 12, 18). Thus, BETi may provide a new of colorectal cancer cells, we identified tripartite motif-containing mechanism to target MYC and other oncogenic transcription fac- protein 33 (TRIM33) as a factor promoting sensitivity to BETi. We tors, which lack obvious binding pockets for small molecules and are demonstrate that loss of TRIM33 reprograms cancer cells to a more thus typically considered to be “undruggable.” resistant state through at least two mechanisms. -
Proteotoxic Stress-Induced Nrf1 Transcriptional Program Requires a Functional TIP60 Complex
bioRxiv preprint doi: https://doi.org/10.1101/443937; this version posted October 16, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Proteotoxic stress-induced Nrf1 transcriptional program requires a functional TIP60 complex Janakiram R. Vangala and Senthil K. Radhakrishnan* Department of Pathology and Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia *Correspondence: Senthil K. Radhakrishnan [email protected] bioRxiv preprint doi: https://doi.org/10.1101/443937; this version posted October 16, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. ABSTRACT In response to inhibition of the cellular proteasome, the transcription factor Nrf1 (also called NFE2L1) induces transcription of proteasome subunit genes resulting in the restoration of proteasome activity and thus enabling the cells to mitigate the proteotoxic stress. To identify novel regulators of Nrf1, we performed an RNA interference screen and discovered that the AAA+ ATPase RUVBL1 is necessary for its transcriptional activity. Given that RUVBL1 is part of different multi-subunit complexes that play key roles in transcription, we dissected this phenomenon further and found that the TIP60 chromatin regulatory complex is essential for Nrf1-dependent transcription of proteasome genes. Consistent with these observations, Nrf1, RUVBL1, and TIP60 proteins were co-recruited to the promoter regions of proteasome genes after proteasome inhibitor treatments. -
16-0352 Technical Data Sheet
Nucleosome, Recombinant Human, H4K5ac dNuc, Biotinylated Catalog No. 16-0352 Lot No. 21147003-61 Pack Size 50 µg Product Description: Mononucleosomes assembled from recombinant human histones expressed in E. coli (two each of histones H2A, H2B, H3 and H4; accession numbers: H2A-P04908; H2B-O60814; H3.1-P68431; H4-P62805) wrapped by 147 base pairs of 601 positioning sequence DNA. Histone H4 (created by a proprietary synthetic method) is N-terminally acetylated and contains acetyl-lysine at position 5. The nucleosome is the basic subunit of chromatin. The 147 bp 601 sequence, identified by Lowary and Widom, has high affinity for histone octamers and is useful for nucleosome assembly. The DNA contains a 5’ biotin-TEG group. Western Blot Data: Western Analysis of Nucleosome, Recombinant Human, H4K5ac. Top Panel: Unmodified H4 Formulation: (Lane 1) and H4K5ac containing nucleosomes (Lane 2) were probed with an anti-H4K5ac antibody and analyzed via ECL Nucleosome, Recombinant Human, H4K5ac (27.3 µg protein readout. Only the H4K5ac sample produced a detectable weight, 50 µg total weight) in 50 µL of 10 mM Tris HCl pH 7.5, signal. Bottom Panel: Detail from Coomassie stained gel 25 mM NaCl, 1 mM EDTA, 2 mM DTT, 20% glycerol. Molarity = showing unmodified H4 nucleosome (Lane 1) and H4K5ac 5 μM. MW = 200,027.9 Da. nucleosome (Lane 2). Storage and Stability: Stable for six months at -80°C from date of receipt. For best results, aliquot and avoid multiple freeze/thaws. Application Notes: H4K5ac dNuc is highly purified and suitable for a variety of applications, including use as a substrate in enzymatic assays or for effector protein binding experiments. -
S41467-019-10037-Y.Pdf
ARTICLE https://doi.org/10.1038/s41467-019-10037-y OPEN Feedback inhibition of cAMP effector signaling by a chaperone-assisted ubiquitin system Laura Rinaldi1, Rossella Delle Donne1, Bruno Catalanotti 2, Omar Torres-Quesada3, Florian Enzler3, Federica Moraca 4, Robert Nisticò5, Francesco Chiuso1, Sonia Piccinin5, Verena Bachmann3, Herbert H Lindner6, Corrado Garbi1, Antonella Scorziello7, Nicola Antonino Russo8, Matthis Synofzik9, Ulrich Stelzl 10, Lucio Annunziato11, Eduard Stefan 3 & Antonio Feliciello1 1234567890():,; Activation of G-protein coupled receptors elevates cAMP levels promoting dissociation of protein kinase A (PKA) holoenzymes and release of catalytic subunits (PKAc). This results in PKAc-mediated phosphorylation of compartmentalized substrates that control central aspects of cell physiology. The mechanism of PKAc activation and signaling have been largely characterized. However, the modes of PKAc inactivation by regulated proteolysis were unknown. Here, we identify a regulatory mechanism that precisely tunes PKAc stability and downstream signaling. Following agonist stimulation, the recruitment of the chaperone- bound E3 ligase CHIP promotes ubiquitylation and proteolysis of PKAc, thus attenuating cAMP signaling. Genetic inactivation of CHIP or pharmacological inhibition of HSP70 enhances PKAc signaling and sustains hippocampal long-term potentiation. Interestingly, primary fibroblasts from autosomal recessive spinocerebellar ataxia 16 (SCAR16) patients carrying germline inactivating mutations of CHIP show a dramatic dysregulation of PKA signaling. This suggests the existence of a negative feedback mechanism for restricting hormonally controlled PKA activities. 1 Department of Molecular Medicine and Medical Biotechnologies, University Federico II, 80131 Naples, Italy. 2 Department of Pharmacy, University Federico II, 80131 Naples, Italy. 3 Institute of Biochemistry and Center for Molecular Biosciences, University of Innsbruck, A-6020 Innsbruck, Austria. -
TRIM33 Antibody Cat
TRIM33 Antibody Cat. No.: 7385 TRIM33 Antibody Immunohistochemistry of TRIM33 in human liver tissue Immunofluorescence of TRIM33 in human liver tissue with with TRIM33 antibody at 2.5 μg/ml. TRIM33 antibody at 20 μg/ml. Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Human, Mouse, Rat TRIM33 antibody was raised against an 18 amino acid peptide near the center of human TRIM33. IMMUNOGEN: The immunogen is located within amino acids 580 - 630 of TRIM33. TESTED APPLICATIONS: ELISA, IF, IHC-P, WB TRIM33 antibody can be used for detection of TRIM33 by Western blot at 1 - 2 μg/mL. APPLICATIONS: Antibody validated: Western Blot in human samples; Immunohistochemistry in human samples and Immunofluorescence in human samples. All other applications and species not yet tested. September 25, 2021 1 https://www.prosci-inc.com/trim33-antibody-7385.html TRIM33 antibody is human, mouse and rat reactive. At least two isoforms of TRIM33 are SPECIFICITY: known to exist. POSITIVE CONTROL: 1) Cat. No. 1304 - Human Liver Tissue Lysate 2) Cat. No. 10-201 - Human Liver Tissue Slide Predicted: 70, 124 kDa PREDICTED MOLECULAR WEIGHT: Observed: 70 kDa Properties PURIFICATION: TRIM33 Antibody is affinity chromatography purified via peptide column. CLONALITY: Polyclonal ISOTYPE: IgG CONJUGATE: Unconjugated PHYSICAL STATE: Liquid BUFFER: TRIM33 Antibody is supplied in PBS containing 0.02% sodium azide. CONCENTRATION: 1 mg/mL TRIM33 antibody can be stored at 4˚C for three months and -20˚C, stable for up to one STORAGE CONDITIONS: year. Additional Info OFFICIAL SYMBOL: TRIM33 TRIM33 Antibody: ECTO, PTC7, RFG7, TF1G, TIF1G, TIFGAMMA, TIF1GAMMA, KIAA1113, E3 ALTERNATE NAMES: ubiquitin-protein ligase TRIM33, Ectodermin homolog, Protein Rfg7 ACCESSION NO.: NP_056990 PROTEIN GI NO.: 74027249 GENE ID: 51592 USER NOTE: Optimal dilutions for each application to be determined by the researcher. -
Genome-Wide Analyses Identify Transcription Factors Required for Proper Morphogenesis of Drosophila Sensory Neuron Dendrites
Downloaded from genesdev.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press Genome-wide analyses identify transcription factors required for proper morphogenesis of Drosophila sensory neuron dendrites Jay Z. Parrish,1 Michael D. Kim,1 Lily Yeh Jan, and Yuh Nung Jan2 Departments of Physiology and Biochemistry, Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA Dendrite arborization patterns are critical determinants of neuronal function. To explore the basis of transcriptional regulation in dendrite pattern formation, we used RNA interference (RNAi) to screen 730 transcriptional regulators and identified 78 genes involved in patterning the stereotyped dendritic arbors of class I da neurons in Drosophila. Most of these transcriptional regulators affect dendrite morphology without altering the number of class I dendrite arborization (da) neurons and fall primarily into three groups. Group A genes control both primary dendrite extension and lateral branching, hence the overall dendritic field. Nineteen genes within group A act to increase arborization, whereas 20 other genes restrict dendritic coverage. Group B genes appear to balance dendritic outgrowth and branching. Nineteen group B genes function to promote branching rather than outgrowth, and two others have the opposite effects. Finally, 10 group C genes are critical for the routing of the dendritic arbors of individual class I da neurons. Thus, multiple genetic programs operate to calibrate dendritic coverage, to coordinate the elaboration of primary versus secondary branches, and to lay out these dendritic branches in the proper orientation. [Keywords: Transcription; RNAi; Drosophila; neuron; dendrite] Supplemental material is available at http://www.genesdev.org. -
RET Inhibition in Novel Patient-Derived Models of RET Fusion
© 2021. Published by The Company of Biologists Ltd | Disease Models & Mechanisms (2021) 14, dmm047779. doi:10.1242/dmm.047779 RESEARCH ARTICLE RET inhibition in novel patient-derived models of RET fusion- positive lung adenocarcinoma reveals a role for MYC upregulation Takuo Hayashi1,2,*,§§, Igor Odintsov1,2,§§, Roger S. Smith1,2,‡,§§, Kota Ishizawa2,§, Allan J. W. Liu3,4, Lukas Delasos3, Christopher Kurzatkowski1, Huichun Tai1,2, Eric Gladstone1,2, Morana Vojnic1,2, Shinji Kohsaka1,2,¶, Ken Suzawa1,**, Zebing Liu1,2,‡‡, Siddharth Kunte3, Marissa S. Mattar5, Inna Khodos6, Monika A. Davare6, Alexander Drilon3, Emily Cheng2, Elisa de Stanchina5, Marc Ladanyi1,2,¶¶,*** and Romel Somwar1,2,¶¶,*** ABSTRACT suppressed by treatment of cell lines with cabozantinib. MYC protein Multi-kinase RET inhibitors, such as cabozantinib and RXDX-105, are levels were rapidly depleted following cabozantinib treatment. Taken active in lung cancer patients with RET fusions; however, the overall together, our results demonstrate that cabozantinib is an effective response rates to these two drugs are unsatisfactory compared to other agent in preclinical models harboring RET rearrangements with three ′ targeted therapy paradigms. Moreover, these inhibitors may have different 5 fusion partners (CCDC6, KIF5B and TRIM33). Notably, we different efficacies against RET rearrangements depending on the identify MYC as a protein that is upregulated by RET expression and upstream fusion partner. A comprehensive preclinical analysis of downregulated by treatment with cabozantinib, opening up potentially the efficacy of RET inhibitors is lacking due to a paucity of disease new therapeutic avenues for the combinatorial targetin of RET fusion- models harboring RET rearrangements. Here, we generated two new driven lung cancers. -
Downregulation of Carnitine Acyl-Carnitine Translocase by Mirnas
Page 1 of 288 Diabetes 1 Downregulation of Carnitine acyl-carnitine translocase by miRNAs 132 and 212 amplifies glucose-stimulated insulin secretion Mufaddal S. Soni1, Mary E. Rabaglia1, Sushant Bhatnagar1, Jin Shang2, Olga Ilkayeva3, Randall Mynatt4, Yun-Ping Zhou2, Eric E. Schadt6, Nancy A.Thornberry2, Deborah M. Muoio5, Mark P. Keller1 and Alan D. Attie1 From the 1Department of Biochemistry, University of Wisconsin, Madison, Wisconsin; 2Department of Metabolic Disorders-Diabetes, Merck Research Laboratories, Rahway, New Jersey; 3Sarah W. Stedman Nutrition and Metabolism Center, Duke Institute of Molecular Physiology, 5Departments of Medicine and Pharmacology and Cancer Biology, Durham, North Carolina. 4Pennington Biomedical Research Center, Louisiana State University system, Baton Rouge, Louisiana; 6Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, New York. Corresponding author Alan D. Attie, 543A Biochemistry Addition, 433 Babcock Drive, Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, (608) 262-1372 (Ph), (608) 263-9608 (fax), [email protected]. Running Title: Fatty acyl-carnitines enhance insulin secretion Abstract word count: 163 Main text Word count: 3960 Number of tables: 0 Number of figures: 5 Diabetes Publish Ahead of Print, published online June 26, 2014 Diabetes Page 2 of 288 2 ABSTRACT We previously demonstrated that micro-RNAs 132 and 212 are differentially upregulated in response to obesity in two mouse strains that differ in their susceptibility to obesity-induced diabetes. Here we show the overexpression of micro-RNAs 132 and 212 enhances insulin secretion (IS) in response to glucose and other secretagogues including non-fuel stimuli. We determined that carnitine acyl-carnitine translocase (CACT, Slc25a20) is a direct target of these miRNAs.