Discovery and Comparative Genomics of All Mouse Protein Kinases
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Gene Symbol Gene Description ACVR1B Activin a Receptor, Type IB
Table S1. Kinase clones included in human kinase cDNA library for yeast two-hybrid screening Gene Symbol Gene Description ACVR1B activin A receptor, type IB ADCK2 aarF domain containing kinase 2 ADCK4 aarF domain containing kinase 4 AGK multiple substrate lipid kinase;MULK AK1 adenylate kinase 1 AK3 adenylate kinase 3 like 1 AK3L1 adenylate kinase 3 ALDH18A1 aldehyde dehydrogenase 18 family, member A1;ALDH18A1 ALK anaplastic lymphoma kinase (Ki-1) ALPK1 alpha-kinase 1 ALPK2 alpha-kinase 2 AMHR2 anti-Mullerian hormone receptor, type II ARAF v-raf murine sarcoma 3611 viral oncogene homolog 1 ARSG arylsulfatase G;ARSG AURKB aurora kinase B AURKC aurora kinase C BCKDK branched chain alpha-ketoacid dehydrogenase kinase BMPR1A bone morphogenetic protein receptor, type IA BMPR2 bone morphogenetic protein receptor, type II (serine/threonine kinase) BRAF v-raf murine sarcoma viral oncogene homolog B1 BRD3 bromodomain containing 3 BRD4 bromodomain containing 4 BTK Bruton agammaglobulinemia tyrosine kinase BUB1 BUB1 budding uninhibited by benzimidazoles 1 homolog (yeast) BUB1B BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast) C9orf98 chromosome 9 open reading frame 98;C9orf98 CABC1 chaperone, ABC1 activity of bc1 complex like (S. pombe) CALM1 calmodulin 1 (phosphorylase kinase, delta) CALM2 calmodulin 2 (phosphorylase kinase, delta) CALM3 calmodulin 3 (phosphorylase kinase, delta) CAMK1 calcium/calmodulin-dependent protein kinase I CAMK2A calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha CAMK2B calcium/calmodulin-dependent -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
High-Resolution Structure of TBP with TAF1 Reveals Anchoring Patterns in Transcriptional Regulation
ARTICLES High-resolution structure of TBP with TAF1 reveals anchoring patterns in transcriptional regulation Madhanagopal Anandapadamanaban1, Cecilia Andresen1,6, Sara Helander1,6, Yoshifumi Ohyama2, Marina I Siponen3,5, Patrik Lundström1, Tetsuro Kokubo2, Mitsuhiko Ikura4, Martin Moche3 & Maria Sunnerhagen1 The general transcription factor TFIID provides a regulatory platform for transcription initiation. Here we present the crystal structure (1.97 Å) and NMR analysis of yeast TAF1 N-terminal domains TAND1 and TAND2 bound to yeast TBP, together with mutational data. We find that yeast TAF1-TAND1, which in itself acts as a transcriptional activator, binds TBP’s concave DNA- binding surface by presenting similar anchor residues to TBP as does Mot1 but from a distinct structural scaffold. Furthermore, we show how TAF1-TAND2 uses an aromatic and acidic anchoring pattern to bind a conserved TBP surface groove traversing the basic helix region, and we find highly similar TBP-binding motifs also presented by the structurally distinct TFIIA, Mot1 and Brf1 proteins. Our identification of these anchoring patterns, which can be easily disrupted or enhanced, provides insight into the competitive multiprotein TBP interplay critical to transcriptional regulation. Initiation of eukaryotic gene transcription at a core promoter requires DNA binding and recruitment of the transcriptional machinery13. the assembly of a preinitiation complex (PIC). These complexes are However, although the DNA anchoring in this model is well estab- biologically dynamic assemblies, and their composition can be altered lished12, recruiting activation-domain complexes have been charac- during development and thereby drive cell-specific programs of tran- terized only at low resolution14–17. Furthermore, although TBP has scription1,2. -
Revealing Transcription Factor and Histone Modification Co-Localization and Dynamics Across Cell Lines by Integrating Chip-Seq A
Zhang et al. BMC Genomics 2018, 19(Suppl 10):914 https://doi.org/10.1186/s12864-018-5278-5 RESEARCH Open Access Revealing transcription factor and histone modification co-localization and dynamics across cell lines by integrating ChIP-seq and RNA-seq data Lirong Zhang1*, Gaogao Xue1, Junjie Liu1, Qianzhong Li1* and Yong Wang2,3,4* From 29th International Conference on Genome Informatics Yunnan, China. 3-5 December 2018 Abstract Background: Interactions among transcription factors (TFs) and histone modifications (HMs) play an important role in the precise regulation of gene expression. The context specificity of those interactions and further its dynamics in normal and disease remains largely unknown. Recent development in genomics technology enables transcription profiling by RNA-seq and protein’s binding profiling by ChIP-seq. Integrative analysis of the two types of data allows us to investigate TFs and HMs interactions both from the genome co-localization and downstream target gene expression. Results: We propose a integrative pipeline to explore the co-localization of 55 TFs and 11 HMs and its dynamics in human GM12878 and K562 by matched ChIP-seq and RNA-seq data from ENCODE. We classify TFs and HMs into three types based on their binding enrichment around transcription start site (TSS). Then a set of statistical indexes are proposed to characterize the TF-TF and TF-HM co-localizations. We found that Rad21, SMC3, and CTCF co-localized across five cell lines. High resolution Hi-C data in GM12878 shows that they associate most of the Hi-C peak loci with a specific CTCF-motif “anchor” and supports that CTCF, SMC3, and RAD2 co-localization serves important role in 3D chromatin structure. -
Therapeutic Potential of TAF1 Bromodomains for Cancer Treatment
bioRxiv preprint doi: https://doi.org/10.1101/394254; this version posted August 17, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Therapeutic potential of TAF1 bromodomains for cancer treatment Veronica Garcia-Carpizo1, Sergio Ruiz-Llorente1, Jacinto Sarmentero1 and Maria J. Barrero1* 1CNIO-Lilly Epigenetics Laboratory Spanish National Cancer Research Center (CNIO), Melchor Fernandez Almagro 3, E-28029 Madrid, Spain *To whom correspondence should be addressed: [email protected] (34) 917 328 000 Keywords: epigenetics, bromodomains, proliferation, cancer Running tittle: TAF1 bromodomains in proliferation 1 bioRxiv preprint doi: https://doi.org/10.1101/394254; this version posted August 17, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. ABSTRACT The discovery of the antiproliferative effects of BRD4 bromodomain inhibitors prompted us to investigate additional bromodomains that might be involved in supporting cellular proliferation. TAF1 is a general transcription factor with two bromodomains that is likely to play important roles in cell viability by supporting transcription. Our work shows that knock down of TAF1 caused antiproliferative effects in several cancer cell lines. Using CRISPR-Cas9 editing techniques we demonstrate that the bromodomains of TAF1 are essential to maintain proliferation of K562 and H322 cells. BAY-299, the best TAF1 bromodomain inhibitor developed so far, also showed antiproliferative effects. BAY-299 caused discrete transcriptional changes that were likely on target but did not correlate with strong effects in cell cycle distribution suggesting that these effects might be, at least in part, mediated by another target. -
Gene Ontology Functional Annotations and Pleiotropy
Network based analysis of genetic disease associations Sarah Gilman Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy under the Executive Committee of the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2014 © 2013 Sarah Gilman All Rights Reserved ABSTRACT Network based analysis of genetic disease associations Sarah Gilman Despite extensive efforts and many promising early findings, genome-wide association studies have explained only a small fraction of the genetic factors contributing to common human diseases. There are many theories about where this “missing heritability” might lie, but increasingly the prevailing view is that common variants, the target of GWAS, are not solely responsible for susceptibility to common diseases and a substantial portion of human disease risk will be found among rare variants. Relatively new, such variants have not been subject to purifying selection, and therefore may be particularly pertinent for neuropsychiatric disorders and other diseases with greatly reduced fecundity. Recently, several researchers have made great progress towards uncovering the genetics behind autism and schizophrenia. By sequencing families, they have found hundreds of de novo variants occurring only in affected individuals, both large structural copy number variants and single nucleotide variants. Despite studying large cohorts there has been little recurrence among the genes implicated suggesting that many hundreds of genes may underlie these complex phenotypes. The question -
Crystal Structure of a TAF1-TAF7 Complex in Human Transcription Factor IID Reveals a Promoter Binding Module
Cell Research (2014) 24:1433-1444. npg © 2014 IBCB, SIBS, CAS All rights reserved 1001-0602/14 $ 32.00 ORIGINAL ARTICLE www.nature.com/cr Crystal structure of a TAF1-TAF7 complex in human transcription factor IID reveals a promoter binding module Hui Wang1, 2, Elizabeth C Curran1, Thomas R Hinds1, 2, Edith H Wang1, Ning Zheng1, 2 1Department of Pharmacology, 2Howard Hughes Medical Institute, Box 357280, University of Washington, Seattle, WA 98195, USA The general transcription factor IID (TFIID) initiates RNA polymerase II-mediated eukaryotic transcription by nucleating pre-initiation complex formation at the core promoter of protein-encoding genes. TAF1, the largest in- tegral subunit of TFIID, contains an evolutionarily conserved yet poorly characterized central core domain, whose specific mutation disrupts cell proliferation in the temperature-sensitive mutant hamster cell line ts13. Although the impaired TAF1 function in the ts13 mutant has been associated with defective transcriptional regulation of cell cycle genes, the mechanism by which TAF1 mediates transcription as part of TFIID remains unclear. Here, we present the crystal structure of the human TAF1 central core domain in complex with another conserved TFIID subunit, TAF7, which biochemically solubilizes TAF1. The TAF1-TAF7 complex displays an inter-digitated compact architecture, featuring an unexpected TAF1 winged helix (WH) domain mounted on top of a heterodimeric triple barrel. The single TAF1 residue altered in the ts13 mutant is buried at the junction of these two structural domains. We show that the TAF1 WH domain has intrinsic DNA-binding activity, which depends on characteristic residues that are commonly used by WH fold proteins for interacting with DNA. -
TAF1 Antibody
For research use only BioVision 09/14 TAF1 Antibody ALTERNATE NAMES: TAF (II) 250, TBP-associated factor 250 kDa, p250, BA2R, CCG1, CCGS, TAF2A CATALOG #: 6845-50 AMOUNT: 50 µl HOST/ISOTYPE: Rabbit Western blot was performed on nuclear IMMUNOGEN: Polyclonal antibody raised in rabbit against human TAF1 extracts from HeLa cells (20 µg) with (TATA box binding protein (TBP)-associated factor; the antibody diluted 1:1,000 in TBS- Transcription initiation factor TFIID subunit 1), using the Tween containing 5% skimmed milk recombinant double bromodomain module of the protein. (Figure 2). The molecular weight marker (in kDa) is shown on the left; FORM: Liquid the location of the protein of interest is indicated on the right. FORMULATION: In PBS with 0.05% (W/V) sodium azide. PURIFICATION: Whole antiserum from rabbit SPECIES REACTIVITY: Human. STORAGE CONDITIONS: Store at -20°C; for long storage, store at -80°C. Avoid multiple freeze-thaw cycles. DESCRIPTION: TAF1 is the largest component and core scaffold of the TFIID basal transcription factor complex which also includes TBP. The protein is able to auto phosphorylate or trans phosphorylate other transcription factors such as TP53 on ‘Thr- 55’, leading to MDM2-mediated degradation of TP53, and GTF2A1 and GTF2F1 on Ser residues. TAF1 possesses DNA- RELATED PRODUCTS: binding activity and is essential for progression of the G1 phase TAF1 bromodomain 1 (1371-1496 aa) (GST-tagged), Human recombinant (Cat # 7660- of the cell cycle. 20, -100) APPLICATION: Western Blot: 1:1000. Note: This information is only intended as a guide. The optimal dilutions must be FOR RESEARCH USE ONLY! Not to be used on humans. -
Host Cell Factors Necessary for Influenza a Infection: Meta-Analysis of Genome Wide Studies
Host Cell Factors Necessary for Influenza A Infection: Meta-Analysis of Genome Wide Studies Juliana S. Capitanio and Richard W. Wozniak Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta Abstract: The Influenza A virus belongs to the Orthomyxoviridae family. Influenza virus infection occurs yearly in all countries of the world. It usually kills between 250,000 and 500,000 people and causes severe illness in millions more. Over the last century alone we have seen 3 global influenza pandemics. The great human and financial cost of this disease has made it the second most studied virus today, behind HIV. Recently, several genome-wide RNA interference studies have focused on identifying host molecules that participate in Influen- za infection. We used nine of these studies for this meta-analysis. Even though the overlap among genes identified in multiple screens was small, network analysis indicates that similar protein complexes and biological functions of the host were present. As a result, several host gene complexes important for the Influenza virus life cycle were identified. The biological function and the relevance of each identified protein complex in the Influenza virus life cycle is further detailed in this paper. Background and PA bound to the viral genome via nucleoprotein (NP). The viral core is enveloped by a lipid membrane derived from Influenza virus the host cell. The viral protein M1 underlies the membrane and anchors NEP/NS2. Hemagglutinin (HA), neuraminidase Viruses are the simplest life form on earth. They parasite host (NA), and M2 proteins are inserted into the envelope, facing organisms and subvert the host cellular machinery for differ- the viral exterior. -
TAF1 Gene TATA-Box Binding Protein Associated Factor 1
TAF1 gene TATA-box binding protein associated factor 1 Normal Function The TAF1 gene provides instructions for making part of a protein called transcription factor IID (TFIID). This protein is active in cells and tissues throughout the body, where it attaches (binds) to DNA. Transcription factor IID plays an essential role in regulating the activity of most genes. The TAF1 gene is part of a complex region of DNA known as the TAF1/DYT3 multiple transcript system. This region consists of short stretches of DNA from the TAF1 gene plus some extra segments of genetic material near the gene. These stretches of DNA can be combined in different ways to create various sets of instructions for making proteins. Researchers believe that some of these variations are critical for the normal function of nerve cells (neurons) in the brain. Health Conditions Related to Genetic Changes X-linked dystonia-parkinsonism Several changes in the TAF1/DYT3 multiple transcript system have been identified in people with X-linked dystonia-parkinsonism. Some alter single DNA building blocks ( nucleotides) in the gene; these changes are described as disease-specific single- nucleotide changes (DSCs). Another genetic change deletes a small number of nucleotides from the gene. Researchers are uncertain how these changes are related to the movement abnormalities characteristic of the disease. X-linked dystonia-parkinsonism may also be related to an extra segment of DNA in the TAF1/DYT3 multiple transcript system. The extra segment results from the insertion of a retrotransposon, which is a small piece of DNA that can move around to different positions in a cell's genetic material. -
Inhibition of ERK 1/2 Kinases Prevents Tendon Matrix Breakdown Ulrich Blache1,2,3, Stefania L
www.nature.com/scientificreports OPEN Inhibition of ERK 1/2 kinases prevents tendon matrix breakdown Ulrich Blache1,2,3, Stefania L. Wunderli1,2,3, Amro A. Hussien1,2, Tino Stauber1,2, Gabriel Flückiger1,2, Maja Bollhalder1,2, Barbara Niederöst1,2, Sandro F. Fucentese1 & Jess G. Snedeker1,2* Tendon extracellular matrix (ECM) mechanical unloading results in tissue degradation and breakdown, with niche-dependent cellular stress directing proteolytic degradation of tendon. Here, we show that the extracellular-signal regulated kinase (ERK) pathway is central in tendon degradation of load-deprived tissue explants. We show that ERK 1/2 are highly phosphorylated in mechanically unloaded tendon fascicles in a vascular niche-dependent manner. Pharmacological inhibition of ERK 1/2 abolishes the induction of ECM catabolic gene expression (MMPs) and fully prevents loss of mechanical properties. Moreover, ERK 1/2 inhibition in unloaded tendon fascicles suppresses features of pathological tissue remodeling such as collagen type 3 matrix switch and the induction of the pro-fbrotic cytokine interleukin 11. This work demonstrates ERK signaling as a central checkpoint to trigger tendon matrix degradation and remodeling using load-deprived tissue explants. Tendon is a musculoskeletal tissue that transmits muscle force to bone. To accomplish its biomechanical function, tendon tissues adopt a specialized extracellular matrix (ECM) structure1. Te load-bearing tendon compart- ment consists of highly aligned collagen-rich fascicles that are interspersed with tendon stromal cells. Tendon is a mechanosensitive tissue whereby physiological mechanical loading is vital for maintaining tendon archi- tecture and homeostasis2. Mechanical unloading of the tissue, for instance following tendon rupture or more localized micro trauma, leads to proteolytic breakdown of the tissue with severe deterioration of both structural and mechanical properties3–5. -
Decreased N-TAF1 Expression in X-Linked Dystonia-Parkinsonism Patient-Specific Neural Stem Cells Naoto Ito1,2,*, William T
© 2016. Published by The Company of Biologists Ltd | Disease Models & Mechanisms (2016) 9, 451-462 doi:10.1242/dmm.022590 RESOURCE ARTICLE Decreased N-TAF1 expression in X-linked dystonia-parkinsonism patient-specific neural stem cells Naoto Ito1,2,*, William T. Hendriks1,2,*, Jyotsna Dhakal1,2, Christine A. Vaine1,2, Christina Liu1,2, David Shin1,2, Kyle Shin1,2, Noriko Wakabayashi-Ito1,2, Marisela Dy1, Trisha Multhaupt-Buell1, Nutan Sharma1, Xandra O. Breakefield1,2,3,‡ and D. Cristopher Bragg1,2,‡ ABSTRACT et al., 2013a). Most cases in which dystonia is the primary clinical manifestation seem to have a genetic predisposition, with over 25 X-linked dystonia-parkinsonism (XDP) is a hereditary neurodegenerative gene loci linked to different forms of the disease (Lohmann and disorder involving a progressive loss of striatal medium spiny neurons. Klein, 2013). Among the many subtypes of dystonia are numerous The mechanisms underlying neurodegeneration are not known, in examples that combine clinical features of Parkinson’s disease part because there have been few cellular models available for (PD), such as (1) DOPA-responsive dystonia, caused by variations studying the disease. The XDP haplotype consists of multiple in genes encoding dopamine biosynthetic enzymes (GCH1, TH, sequence variations in a region of the X chromosome containing SR; Lee and Jeon, 2014); (2) rapid-onset dystonia-parkinsonism TAF1, a large gene with at least 38 exons, and a multiple transcript (RDP), caused by variations in a subunit of the sodium/potassium system (MTS) composed of five unconventional exons. A previous ATPase (ATP1A3; Geyer and Bressman, 2011); (3) DYT16 study identified an XDP-specific insertion of a SINE-VNTR-Alu dystonia, associated with variations in the PKR regulatory (SVA)-type retrotransposon in intron 32 of TAF1, as well as a neural- protein, PACT (PRKRA; Zech et al., 2014; Camargos et al., specific TAF1 isoform, N-TAF1, which showed decreased expression 2012); and (4) other degenerative disorders such as Wilson’s in post-mortem XDP brain compared with control tissue.