The Aging Vasculature: Glucose Tolerance, Hypoglycemia and the Role of the Serum Response Factor

Total Page:16

File Type:pdf, Size:1020Kb

The Aging Vasculature: Glucose Tolerance, Hypoglycemia and the Role of the Serum Response Factor Journal of Cardiovascular Development and Disease Review The Aging Vasculature: Glucose Tolerance, Hypoglycemia and the Role of the Serum Response Factor Hazel Aberdeen 1, Kaela Battles 2, Ariana Taylor 2, Jeranae Garner-Donald 2, Ana Davis-Wilson 2, Bryan T. Rogers 2, Candice Cavalier 2 and Emmanuel D. Williams 2,* 1 Department of Biomedical Sciences, Baptist Health Sciences University, Memphis, TN 38103, USA; hazel.aberdeen@bchs.edu or hazel.aberdeen@bmhcc.org 2 Department of Biology and Chemistry, Southern University and A&M College, Baton Rouge, LA 70813, USA; kaela_battles_00@subr.edu (K.B.); ariana_taylor_00@subr.edu (A.T.); jeranae_garner-don00@subr.edu (J.G.-D.); ana.davis@sus.edu (A.D.-W.); Bryan_Rogers@subr.edu (B.T.R.); candice_cavalier@subr.edu (C.C.) * Correspondence: emmanuel.williams@subr.edu Abstract: The fastest growing demographic in the U.S. at the present time is those aged 65 years and older. Accompanying advancing age are a myriad of physiological changes in which reserve capacity is diminished and homeostatic control attenuates. One facet of homeostatic control lost with advancing age is glucose tolerance. Nowhere is this more accentuated than in the high proportion of older Americans who are diabetic. Coupled with advancing age, diabetes predisposes affected subjects to the onset and progression of cardiovascular disease (CVD). In the treatment of type 2 diabetes, hypoglycemic episodes are a frequent clinical manifestation, which often result in more severe pathological outcomes compared to those observed in cases of insulin resistance, including premature appearance of biomarkers of senescence. Unfortunately, molecular mechanisms of hy- poglycemia remain unclear and the subject of much debate. In this review, the molecular basis of Citation: Aberdeen, H.; Battles, K.; the aging vasculature (endothelium) and how glycemic flux drives the appearance of cardiovascular Taylor, A.; Garner-Donald, J.; lesions and injury are discussed. Further, we review the potential role of the serum response factor Davis-Wilson, A.; Rogers, B.T.; (SRF) in driving glycemic flux-related cellular signaling through its association with various proteins. Cavalier, C.; Williams, E.D. The Aging Vasculature: Glucose Keywords: aging; serum response factor; vascular; glucose; hypoglycemia; heart Tolerance, Hypoglycemia and the Role of the Serum Response Factor. J. Cardiovasc. Dev. Dis. 2021, 8, 58. https://doi.org/10.3390/jcdd8050058 1. Introduction The exponential expansion of the older adult demographic (65 and older) in the United Received: 8 January 2021 States is unique in the nation’s history. By the midpoint of the twenty-first century, it is Accepted: 23 March 2021 estimated that Americans aged 65 or older will number approximately 90 million people, Published: 17 May 2021 and the number of older Americans just merely a decade into the twenty-first century will nearly double [1]. Publisher’s Note: MDPI stays neutral The rapid aging of the United States population is influenced by two primary factors: with regard to jurisdictional claims in published maps and institutional affil- (1) Americans are living longer than in previous decades and (2) there are more older iations. adults aged 65 and older than in previous generations, post-World War II. Americans are now living beyond their 70s, with many achieving centenarian status. The oldest of the “baby boomers” reached age 65 in 2011, setting off a phenomenon in the United States not previously observed. Since the start of 2011, and every day for the next 15 to 20 years, approximately 8000–10,000 Americans will observe their 65th birthday. In Copyright: © 2021 by the authors. the year 2030, when the last baby boomer turns 65, the demographic makeup of our Licensee MDPI, Basel, Switzerland. country will have changed greatly. Moreover, it is estimated that twenty percent of all This article is an open access article distributed under the terms and Americans—approximately 77 million people—will be aged 65 years or older [2]. conditions of the Creative Commons The aging demographic has had a widespread impact on essentially every component Attribution (CC BY) license (https:// of American society. At each transition from one life stage to the next in the lifespan of creativecommons.org/licenses/by/ those born after World War II, the United States has been impacted by their increased 4.0/). numbers and needs—from robust demand in commercial adolescent products as they J. Cardiovasc. Dev. Dis. 2021, 8, 58. https://doi.org/10.3390/jcdd8050058 https://www.mdpi.com/journal/jcdd J. Cardiovasc. Dev. Dis. 2021, 8, x FOR PEER REVIEW 2 of 21 The aging demographic has had a widespread impact on essentially every compo- nent of American society. At each transition from one life stage to the next in the lifespan of those born after World War II, the United States has been impacted by their increased J. Cardiovasc. Dev. Dis. 2021, 8, 58 2 of 20 numbers and needs—from robust demand in commercial adolescent products as they entered into their teen years during the late 1940s and 1950s, to the infrastructural im- pacts via construction of thousands of new schools during the following decades, to the housingentered intoboom their of teenthe 1970s. years duringModern the times late 1940sdemon andstrate 1950s, that to the the baby infrastructural boomer’s popula- impacts tionvia constructioncontinues to ofexercise thousands its influence. of new schools Unquestionably, during the this following occurrence decades, will to have the housingits most significantboom of the impact 1970s. Modernon United times States demonstrate public health that the care baby systems. boomer’s Public population health continuesplays an essentialto exercise role its in influence. supporting Unquestionably, those in dire thisneed, occurrence bridging patients will have and its mostcommunities significant to availableimpact on resources, United States and publicequally health important, care systems. promoting Public healthy health aging plays anbecause essential of its role im- in pactsupporting on environmental those in dire factors. need, The bridging public patients health sector and communities is readily well-positioned to available resources, to meet theand growing equally needs important, and demands promoting of healthya rapidly aging aging because nation of[2–4]. its impact on environmental factors.During The publicthe last health half of sector the twentieth is readily centur well-positionedy, robust health to meet care the initiatives growing needsand rapid and advancesdemands in of therapeutic a rapidly aging treatment nation led [2– 4in]. part to an increase in average life expectancy in the UnitedDuring States. the last This half nearly of the 30 twentieth year gain century, in life expectancy robust health within care a initiatives hundred-year and rapidspan hadadvances never inbeen therapeutic observed. treatment Many of led the in pathol part toogies an increasethat claimed in average our inhabitants life expectancy of pre- in viousthe United generations, States. Thisincluding nearly polio 30 year and gain typhoid, in life expectancycease to be withinthe “doom a hundred-year and gloom” span di- agnosishad never that been they observed. once were Many at the of theturn pathologies of the century. that claimed While these our inhabitants “threats of of old” previous rou- tinelygenerations, present including significant polio health and challenges typhoid, cease in the to beUnited the “doom States, and these gloom” manifestations diagnosis thatare nothey longer once the were morbidity at the turn and of mortality the century. threat While in adults these“threats they once of old”were. routinely However, present other significant health challenges in the United States, these manifestations are no longer the pathologies have continued to be staples in the leading causes of death among Ameri- morbidity and mortality threat in adults they once were. However, other pathologies have cans. Since 1909, heart disease has been the leading cause of death among American continued to be staples in the leading causes of death among Americans. Since 1909, heart adults every year except in the period 1918–1920, when the Spanish Flu epidemic oc- disease has been the leading cause of death among American adults every year except in curred [4]. Moreover, since 1935, cancer has been the next leading cause of mortality in the period 1918–1920, when the Spanish Flu epidemic occurred [4]. Moreover, since 1935, Americans [5]. cancer has been the next leading cause of mortality in Americans [5]. According to the 2018 Centers for Disease Control & Prevention, both cancer and According to the 2018 Centers for Disease Control & Prevention, both cancer and heart heart disease risks are increased with advancing age (Figure 1; [6]). disease risks are increased with advancing age (Figure1;[6]). Figure 1. The 2018 Center for Disease Control and Prevention report on the leading causes of death from 2017 to 2018. 1 Figure 1. The 2018 Center for Disease Control and Prevention report on the leading causes of death from 2017 to 2018. 1 Statistically significant decrease in age-adjusted death rate from 2017 to 2018 (p < 0.05).2 Statistically significant increase Statistically significant decrease in age-adjusted death rate from 2017 to 2018 (p < 0.05).2 Statistically significant increase in in age-adjusted death rate from 2017 to 2018 (p < 0.05).NOTES: A total of 2,839,205 resident deaths were registered in the age-adjusted death rate from 2017 to 2018 (p < 0.05).NOTES: A total of 2,839,205 resident deaths were registered in the United States in 2018. The The 10 10 leading leading causes of death accounted for 73.8% of all deaths in the United States in 2018. Causes Causes of death are ranked according to number of deaths. Rankings for 2018 were the same as in 2017. Data table for Figure2 includes the number of deaths for leading causes. J. Cardiovasc. Dev. Dis. 2021, 8, 58 3 of 20 J. Cardiovasc. Dev. Dis. 2021, 8, x FOR PEER REVIEW 4 of 21 Figure 2.
Loading...
Loading...
Loading...
Loading...
Loading...

15 pages remaining, click to load more.

Recommended publications
  • Inhibitor of Differentiation 4 (ID4) Represses Myoepithelial Differentiation Of
    bioRxiv preprint doi: https://doi.org/10.1101/2020.04.06.026963; this version posted April 6, 2020. 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. 1 Inhibitor of Differentiation 4 (ID4) represses myoepithelial differentiation of 2 mammary stem cells through its interaction with HEB 3 Holly Holliday1,2, Daniel Roden1,2, Simon Junankar1,2, Sunny Z. Wu1,2, Laura A. 4 Baker1,2, Christoph Krisp3,4, Chia-Ling Chan1, Andrea McFarland1, Joanna N. Skhinas1, 5 Thomas R. Cox1,2, Bhupinder Pal5, Nicholas Huntington6, Christopher J. Ormandy1,2, 6 Jason S. Carroll7, Jane Visvader5, Mark P. Molloy3, Alexander Swarbrick1,2 7 1. The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, 8 NSW 2010, Australia 9 2. St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 10 2010, Australia 11 3. Australian Proteome Analysis Facility, Macquarie University, Sydney, NSW 12 2109, Australia 13 4. Institute of Clinical Chemistry and Laboratory Medicine, Mass Spectrometric 14 Proteomics, University Medical Center Hamburg-Eppendorf, Hamburg 20251, 15 Germany 16 5. ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of 17 Medical Research, Parkville, Victoria 3052, Australia 18 6. Biomedicine Discovery Institute, Department of Biochemistry and Molecular 19 Biology, Monash University, Clayton, VIC 3168, Australia 20 7. Cancer Research UK Cambridge Institute, University of Cambridge, Robinson 21 Way, Cambridge CB2 0RE, UK 22 bioRxiv preprint doi: https://doi.org/10.1101/2020.04.06.026963; this version posted April 6, 2020.
    [Show full text]
  • Expression of Oncogenes ELK1 and ELK3 in Cancer
    Review Article Annals of Colorectal Cancer Research Published: 11 Nov, 2019 Expression of Oncogenes ELK1 and ELK3 in Cancer Akhlaq Ahmad and Asif Hayat* College of Chemistry, Fuzhou University, China Abstract Cancer is the uncontrolled growth of abnormal cells anywhere in a body, ELK1 and ELK3 is a member of the Ets-domain transcription factor family and the TCF (Ternary Complex Factor) subfamily. Proteins in this subfamily regulate transcription when recruited by SRF (Serum Response Factor) to bind to serum response elements. ELK1 and ELK3 transcription factors are known as oncogenes. Both transcription factors are proliferated in a different of type of cancer. Herein, we summarized the expression of transcription factor ELK1 and ELK3 in cancer cells. Keywords: ETS; ELK1; ELK3; Transcription factor; Cancer Introduction The ETS, a transcription factor of E twenty-six family based on a dominant ETS amino acids that integrated with a ~10-basepair element arrange in highly mid core sequence 5′-GGA(A/T)-3′ [1-2]. The secular family alter enormous 28/29 members which has been assigned in human and mouse and similarly the family description are further sub-divided into nine sub-families according to their homology and domain factor [3]. More importantly, one of the subfamily members such as ELK (ETS-like) adequate an N-terminal ETS DNA-binding domain along with a B-box domain that transmit the response of serum factor upon the formation of ternary complex and therefore manifested as ternary complex factors [4]. Further the ELK sub-divided into Elk1, Elk3 (Net, Erp or Sap2) and Elk4 (Sap1) proteins [3,4], which simulated varied proportional of potential protein- protein interactions [4,5].
    [Show full text]
  • Interaction and Functional Cooperation of the Cancer-Amplified Transcriptional Coactivator Activating Signal Cointegrator-2 and E2F-1 in Cell Proliferation
    948 Vol. 1, 948–958, November 2003 Molecular Cancer Research Interaction and Functional Cooperation of the Cancer-Amplified Transcriptional Coactivator Activating Signal Cointegrator-2 and E2F-1 in Cell Proliferation Hee Jeong Kong,1 Hyun Jung Yu,2 SunHwa Hong,2 Min Jung Park,2 Young Hyun Choi,3 Won Gun An,4 Jae Woon Lee,5 and JaeHun Cheong2 1Laboratory of Molecular Growth Regulation, National Institute of Health, Bethesda, MD; 2Department of Molecular Biology, Pusan National University, Busan, Republic of Korea; 3Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Busan, Republic of Korea; 4Department of Biology, Kyungpook National University, DaeGu, Republic of Korea; and 5Department of Medicine/Endocrinology, Baylor College of Medicine Houston, TX. Abstract structure and recruitment of a transcription initiation complex Activating signal cointegrator-2 (ASC-2), a novel coac- containing RNA polymerase II to the promoter (1). Recent tivator, is amplified in several cancer cells and known to studies have shown that DNA-bound transcriptional activator interact with mitogenic transcription factors, including proteins accomplish these two tasks with the assistance of a serum response factor, activating protein-1, and nuclear class of proteins called transcriptional coactivators (2, 3). They factor-KB, suggesting the physiological role of ASC-2 in may be thought of as adaptors or components in a signaling the promotion of cell proliferation. Here, we show that pathway that transmits transcriptional activation signals from the expression pattern of ASC-2 was correlated with that DNA-bound activator proteins to the chromatin and transcrip- of E2F-1 for protein increases at G1 and S phase.
    [Show full text]
  • Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development
    International Journal of Molecular Sciences Review Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development Charles Ducker * and Peter E. Shaw * Queen’s Medical Centre, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK * Correspondence: charles.ducker1@nottingham.ac.uk (C.D.); peter.shaw1@nottingham.ac.uk (P.E.S.) Abstract: Genome expansion, whole genome and gene duplication events during metazoan evolution produced an extensive family of ETS genes whose members express transcription factors with a conserved winged helix-turn-helix DNA-binding domain. Unravelling their biological roles has proved challenging with functional redundancy manifest in overlapping expression patterns, a common consensus DNA-binding motif and responsiveness to mitogen-activated protein kinase signalling. Key determinants of the cellular repertoire of ETS proteins are their stability and turnover, controlled largely by the actions of selective E3 ubiquitin ligases and deubiquitinases. Here we discuss the known relationships between ETS proteins and enzymes that determine their ubiquitin status, their integration with other developmental signal transduction pathways and how suppression of ETS protein ubiquitination contributes to the malignant cell phenotype in multiple cancers. Keywords: E3 ligase complex; deubiquitinase; gene fusions; mitogens; phosphorylation; DNA damage 1. Introduction Citation: Ducker, C.; Shaw, P.E. Cell growth, proliferation and differentiation are complex, concerted processes that Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer rely on careful regulation of gene expression. Control over gene expression is maintained and Development. Int. J. Mol. Sci. through signalling pathways that respond to external cellular stimuli, such as growth 2021, 22, 5119. https://doi.org/ factors, cytokines and chemokines, that invoke expression profiles commensurate with 10.3390/ijms22105119 diverse cellular outcomes.
    [Show full text]
  • MRTF: Basic Biology and Role in Kidney Disease
    International Journal of Molecular Sciences Review MRTF: Basic Biology and Role in Kidney Disease Maria Zena Miranda 1, Zsuzsanna Lichner 1, Katalin Szászi 1,2 and András Kapus 1,2,3,* 1 Keenan Research Centre for Biomedical Science of the St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada; zena.miranda@mail.utoronto.ca (M.Z.M.); zsuzsanna.lichner@unityhealth.to (Z.L.); katalin.szaszi@unityhealth.to (K.S.) 2 Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada 3 Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada * Correspondence: andras.kapus@unityhealth.to Abstract: A lesser known but crucially important downstream effect of Rho family GTPases is the regulation of gene expression. This major role is mediated via the cytoskeleton, the organization of which dictates the nucleocytoplasmic shuttling of a set of transcription factors. Central among these is myocardin-related transcription factor (MRTF), which upon actin polymerization translocates to the nucleus and binds to its cognate partner, serum response factor (SRF). The MRTF/SRF complex then drives a large cohort of genes involved in cytoskeleton remodeling, contractility, extracellular matrix organization and many other processes. Accordingly, MRTF, activated by a variety of mechanical and chemical stimuli, affects a plethora of functions with physiological and pathological relevance. These include cell motility, development, metabolism and thus metastasis formation, inflammatory responses and—predominantly-organ fibrosis. The aim of this review is twofold: to provide an up- to-date summary about the basic biology and regulation of this versatile transcriptional coactivator; and to highlight its principal involvement in the pathobiology of kidney disease.
    [Show full text]
  • Expression of C-Fos, Tyrosine Hydroxylase, and Neuropeptide
    0031-399819513701-0015$03.0010 PEDIATRIC RESEARCH Vol. 37, No. 1, 1995 Copyright O 1994 International Pediatric Research Foundation, Inc. Printed in U.S.A. Expression of e-fos, Tyrosine Hydroxylase, and Neuropeptide mRNA in the Rat Brain around Birth: Effects of Hypoxia and Hypothermia THOMAS RINGSTEDT, LIE-QI TANG, J&hAN PERSSON,' URBAN LENDAHL, AND HUGOLAGERCRANTZ Department of Biochemistry, Laboratory of Molecular Neurobiology [T.R., H.P.], Department of Woman & Child Health [T.R., L.-Q.T., H.L.], and Department of Cell and Molecular Biology [U.L.], Karolinska Institute, Stockholm, Sweden Arousal at birth is likely to be accompanied by changes in augmented by hypoxia and hypothermia. The expression patterns gene expression patterns in the brain. We analyzed the expres- of the other genes were not significantly altered, with the excep- sion levels of genes that may be involved in neonatal adaptation. tion of a very slight increase in tyrosine hydroxylase RNA levels. We have also tried to dissect the effect of hypoxia and hypother- We discuss tentative mechanisms for the transient increase in mia, two components that may play a role in gene expression at c-jos expression and the possible involvement of catecholamines birth. Therefore, we analyzed the expression patterns of the c-fos, in this process. (Pediatr Res 37: 15-20, 1995) tyrosine hydroxylase, enkephalin, preprotachykinin-A, and neu- ropeptide Y genes in various brain regions of rat pups at various Abbreviations time points after cesarean section under normal conditions and TH, tyrosine hydroxylase after exposure to hypoxia and hypothermia. We found that c-jos PI, P2 etc., number of days after birth RNA was up-regulated transiently after birth in neocortex, mid- PPT-A, preprotachykinin-A brain, and pons-medulla with a maximum of 30 min after cesar- NPY, neuropeptide Y ean section, and that this transient increase was not further d.p.c., days postcoitum Birth represents a major transition in many important body in nonrespiratory brain nuclei around birth (6).
    [Show full text]
  • The Role of Gata2 in Hematopoietic and Vascular Development By
    The Role of Gata2 in Hematopoietic and Vascular Development by William D Brandt A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Cellular and Molecular Biology) in The University of Michigan 2009 Doctoral Committee: Professor James Douglas Engel, Chair Professor Eric R Fearon Professor Deborah L Gumucio Associate Professor Thomas M Glaser William D Brandt 2009 Dedication To my family, without whom this PhD would never have been possible. ii Acknowledgements The Engel lab and the University of Michigan will always have my deepest gratitude, particularly the lab’s proprietor and my thesis advisor Doug Engel, whose love of science and good nature has always been a source of inspiration. Doug has been instrumental in my growth as a nascent scientist and I will forever be indebted to him. My gratitude also goes to Kim-Chew Lim and Tomo Hosoya, whose wealth of knowledge and support were relied upon regularly. To Deb Gumucio, Tom Glaser, and Eric Fearon, whose advice and support facilitated my maturation from a naïve student to a proficient scientist – thank you. And to Lori Longeway and Kristin Hug, whose capabilities as department representatives I repeatedly put to the test; you came through for me every time. Thank you. Finally, no amount of words can express how truly grateful and indebted I am to my parents and sister – Cary, Kim, and Jenelle. I would not be in this position today without their unerring love and support. iii Table of Contents Dedication ii Acknowledgements iii List of Figures v List of Tables vi Abstract vii Chapter 1.
    [Show full text]
  • Crkii Induces Serum Response Factor Activation and Cellular Transformation Through Its Function in Rho Activation
    Oncogene (2003) 22, 5946–5957 & 2003 Nature Publishing Group All rights reserved 0950-9232/03 $25.00 www.nature.com/onc CrkII induces serum response factor activation and cellular transformation through its function in Rho activation Toshinori Iwahara1, Tsuyoshi Akagi1, Tomoyuki Shishido1 and Hidesaburo Hanafusa*,1 1Laboratory of Molecular Oncology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan CrkII belongs to the adaptor protein family that plays a interesting biological activities despite the lack of an crucial role in signal transduction. In order to better enzymatic domain. For example, v-Crk induces onco- understand the biological functions of CrkII, we focused genic transformation of chicken embryo fibroblasts on the regulation of gene expression by CrkII. Various (CEF) and the elevation of tyrosine phosphorylation transcriptional control elements were examined for their levels of several proteins (Birge et al., 1996; Feller, activation by CrkII-expression, and we found that CrkII 2001). CrkL, which has a similar structure to CrkII, has selectively activates the serum response element (SRE), a also been reported to induce the anchorage independent transcriptional control element of immediate-early genes. growth of Rat1 cells. Even though cellular CrkII has not This SRE activation induced by CrkII-overexpression was been reported to have oncogenic potential, it has been mediated by the serum response factor (SRF) via Rho. shown to regulate several biological activities, including Indeed, we confirmed that the amount of activated Rho mitogenesis and reorganization of the cytoskeleton was increased in the CrkII-expressing cells. Moreover, we (Klemke et al., 1998; Nakashima et al., 1999; Cho and showed that when overexpressed, CrkII induces the Klemke, 2000; Gumienny et al., 2001).
    [Show full text]
  • ERP, a New Member of the Ets Transcription Factor/Oncoprotein
    MOLECULAR AND CELLULAR BIOLOGY, May 1994, p. 3292-3309 Vol. 14, No. 5 0270-7306/94/$04.00+0 Copyright © 1994, American Society for Microbiology ERP, a New Member of the ets Transcription Factor/Oncoprotein Family: Cloning, Characterization, and Differential Expression during B-Lymphocyte Development MONICA LOPEZ, PETER OETTGEN, YASMIN AKBARALI, ULRICH DENDORFER, AND TOWIA A. LIBERMANN* Department of Medicine, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts 02215 Received 23 July 1993/Returned for modification 18 January 1994/Accepted 17 February 1994 The ets gene family encodes a group of proteins which function as transcription factors under physiological conditions and, if aberrantly expressed, can cause cellular transformation. We have recently identified two regulatory elements in the murine immunoglobulin heavy-chain (IgH) enhancer, TT and ,uB, which exhibit striking similarity to binding sites for ets-related proteins. To identify ets-related transcriptional regulators expressed in pre-B lymphocytes that may interact with either the w or the ,uB site, we have used a PCR approach with degenerate oligonucleotides encoding conserved sequences in all members of the ets family. We have cloned the gene for a new ets-related transcription factor, ERP (ets-related protein), from the murine pre-B cell line BASC 6C2 and from mouse lung tissue. The ERP protein contains a region of high homology with the ETS DNA-binding domain common to all members of the ets transcription factor/oncoprotein family. Three additional smaller regions show homology to the ELK-1 and SAP-1 genes, a subgroup of the ets gene family that interacts with the serum response factor.
    [Show full text]
  • Supplement. Transcriptional Factors (TF), Protein Name and Their Description Or Function
    Supplement. Transcriptional factors (TF), protein name and their description or function. TF Protein name TF description/function ARID3A AT rich interactive domain 3A (BRIGHT-like) This gene encodes a member of the ARID (AT-rich interaction domain) family of DNA binding proteins. ATF4 Activating Transcription Factor 4 Transcriptional activator. Binds the cAMP response element (CRE) (consensus: 5-GTGACGT[AC][AG]-3), a sequence present in many viral and cellular promoters. CTCF CCCTC-Binding Factor Chromatin binding factor that binds to DNA sequence specific sites. Involved in transcriptional regulation by binding to chromatin insulators and preventing interaction between promoter and nearby enhancers and silencers. The protein can bind a histone acetyltransferase (HAT)-containing complex and function as a transcriptional activator or bind a histone deacetylase (HDAC)-containing complex and function as a transcriptional repressor. E2F1-6 E2F transcription factors 1-6 The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. EBF1 Transcription factor COE1 EBF1 has been shown to interact with ZNF423 and CREB binding proteins.
    [Show full text]
  • Inositol Polyphosphate Multikinase Is a Coactivator for Serum Response Factor-Dependent Induction of Immediate Early Genes
    Inositol polyphosphate multikinase is a coactivator for serum response factor-dependent induction of immediate early genes Eunha Kima,1, Richa Tyagib,1, Joo-Young Leea, Jina Parka, Young-ran Kima, Jiyoon Beona, Po Yu Chenb, Jiyoung Y. Chab, Solomon H. Snyderb,c,d,2, and Seyun Kima,e,2 aDepartment of Biological Sciences and eKAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea; and bThe Solomon H. Snyder Department of Neuroscience, cDepartment of Psychiatry and Behavioral Sciences, and dDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 Contributed by Solomon H. Snyder, November 1, 2013 (sent for review August 13, 2013) Inositol polyphosphate multikinase (IPMK) is a notably pleiotropic We monitored expression of RNA for a wide range of genes in protein. It displays both inositol phosphate kinase and phospha- a microarray analysis in wild-type and IPMK-deleted mouse tidylinositol kinase catalytic activities. Noncatalytically, IPMK stabil- embryonic fibroblasts (MEFs) in the presence of serum (Fig. 1 izes the mammalian target of rapamycin complex 1 and acts as a and Fig. S1A). Over 1,400 genes are down-regulated by IPMK transcriptional coactivator for CREB-binding protein/E1A binding deletion whereas 767 are up-regulated. Among the down-regulated protein p300 and tumor suppressor protein p53. Serum response genes are a substantial number of immediate early genes that factor (SRF) is a major transcription factor for a wide range of contain serum response element (SRE) in their promoters and immediate early genes. We report that IPMK, in a noncatalytic are well-known as SRF targets (Fig.
    [Show full text]
  • The Inner Core of the Serum Response Element Mediates Both the Rapid Induction and Subsequent Repression of C-Los Transcription Following Serum Stimulation
    Downloaded from genesdev.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press The inner core of the serum response element mediates both the rapid induction and subsequent repression of c-los transcription following serum stimulation Victor M. Rivera, Morgan Sheng, and Michael E. Greenberg 1 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115 USA Serum stimulation of quiescent fibroblasts results in a dramatic increase in c-fos transcription that peaks by 15 min and is then rapidly repressed to basal levels within 60 min. Using a nuclear run-on assay to follow directly the kinetics of transcription of mutant c-fos constructs, we demonstrate that the serum response element (SRE) is the site of regulation of both the induction and repression events. This is indicated by the ability of the SRE to mediate c-fos kinetics of induced transcription when fused to a heterologous gene and in the absence of a recognizable TATA element. Functions of the inner core and the outer palindromic arms of the SRE have been determined by mutagenesis. The 14-bp inner core binds the serum response factor (SRF) and is, itself, sufficient to mediate both the induction and shutoff of serum-stimulated transcription. Therefore, SRF and any other factors that regulate the transient kinetics of c-fos transcription require no more than these 14 nucleotides to function. The palindromic outer arms of the SRE stabilize the binding of SRF and thereby enhance the transcriptional response to serum. Autoregulation by the c-fos gene product is not affected by the direct interaction of Fos/Jun complexes with the c-fos promoter and is likely to be mediated by either a novel function of the Fos protein or by an effect of Fos on the expression of another gene.
    [Show full text]