DOCSLIB.ORG

PDF Document

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
PDF Document Acta Chim. Slov. 2008, 55, 53–57 53 Mini review Multiple Signaling Pathways Coordinate CYP17 Gene Expression in the Human Adrenal Cortex Marion B. Sewer*, Donghui Li, Eric B. Dammer, Srinath Jagarlapudi and Natasha Lucki School of Biology and Parker H. Petit Institute for Bioengineering & Biosciences, Georgia Institute of Technology, Atlanta, GA 30332-0230 * Corresponding author: [email protected] Received: 17-09-2007 Abstract Optimal levels of steroid hormone biosynthesis are assured by the integration of several regulatory mechanisms, includ- ing substrate delivery, enzymatic activity, and gene transcription. In the human adrenal cortex, optimal glucocorticoid secretion is achieved by the actions of adrenocorticotropin (ACTH), which exerts transcriptional pressure on all genes involved in steroidogenesis. One of these genes is CYP17, which encodes P450 17α-hydroxylase-17,20 lyase, a key en- zyme in the production of cortisol and adrenal androgens. Levels of CYP17 transcription are regulated by multiple reg- ulatory mechanisms that act to respond to various signaling cues. These cues are coordinated in a developmental, species-, and tissue-specific manner, with an additional time/circadian-dependent level of regulation. This brief review will highlight some of the signal transduction cascades and transcription factors that have been shown to modulate CYP17 gene expression in the adrenal cortex. Keywords: CYP17, adrenocorticotropin, angiotensin II, cAMP, steroid hydroxylase, steroidogenic factor-1, PKA 1. Overview sponse, and is produced in the zona fasciculata. This re- view will focus on the transcriptional regulation of Steroid hormones exert control of diverse physiologi- CYP17. CYP17 is localized in the endoplasmic reticulum cal processes by serving as ligands for intracellular and and catalyzes both the 17-hydroxylation of pregnenolone plasma membrane receptors. While ligand binding to and progesterone and the 17,20 bond scission of 17- plasma membrane receptors is coupled to the rapid activa- hydroxypregnenolone and 17-hydroxyprogesterone. Be- tion of signaling pathways, hormone-bound intracellular cause the hydroxylase activity is required for glucocorti- receptors are transcription factors, and thus alter gene ex- coid production and both the hydroxylase and lyase activ- pression by binding to DNA response elements. Cortisol, ities are essential for adrenal androgen biosynthesis, the aldosterone, and adrenal androgens are the primary bioac- activities of this enzyme are positioned to direct hormone tive steroid hormones that are produced in the human ad- identity and adrenal output. renal cortex. Like all classes of steroid hormones, biosyn- thesis occurs in a multi-step process and requires the ac- tions of both members of the cytochrome P450 monooxy- 2. Signaling Pathways genase superfamily, as well as hydroxysteroid dehydroge- nases. These enzymes catalyze the conversion of choles- Steroidogenic capacity is governed by peptide hor- terol to aldosterone, cortisol, or adrenal androgens in a mones that are secreted by the anterior pituitary in re- zone-specific manner. Aldosterone, a mineralocorticoid, sponse to signaling from the hypothalamus. These peptide is a key regulator of sodium and potassium homeostasis molecules evoke changes in steroid hormone output by and is produced in the zona glomerulosa, whereas adrenal acting as ligands for G protein-coupled receptors. Al- androgens are synthesized in the zona reticularis. The glu- though numerous signaling molecules have been implicat- cocorticoid cortisol directs carbohydrate metabolism, as ed as regulators of steroidogenic gene transcription in the well as modulates blood pressure and the immune re- adrenal cortex,1 the most important factor in glucocorti- Sewer et al.: Multiple Signaling Pathways Coordinate CYP17 Gene Expression ... 54 Acta Chim. Slov. 2008, 55, 53–57 coid production and CYP17 regulation is ACTH.2–7 This transfection of a constitutively active β-catenin mutant in peptide hormone promotes steroidogenesis by activating H295R cells both induced StAR reporter gene activity, intracellular signaling pathways that facilitate cholesterol adding to a rapidly expanding list of signaling molecules uptake, transport, and delivery,8,9 and induce steroidogenic that modulate adrenocortical steroidogenesis.31 Given that gene transcription.2,10–14 The trophic actions of ACTH are SF-1 synergizes with β-catenin in the activation of the rat multi-faceted and allow for rapid production of steroid inhibin alpha gene during adrenal development,32 it is hormones by increasing substrate availability and sus- likely that Wnt-dependent signaling cascades will be tained biosynthetic capacity by inducing gene expression. found to play other critical roles in steroidogenesis, not Perhaps the most widely studied pathway is the cAMP only in the adrenal gland, but in other steroidogenic tis- signaling cascade. ACTH binding to the melanocortin 2 sues as well. Additionally, the cloning and functional receptor results in the activation of the adenylyl cyclase, characterization of T-cell factor 4N has revealed that this increased intracellular cAMP and activation of the cAMP- transcription factor synergizes with β-catenin and SF-1 in dependent protein kinase (PKA). PKA then acts to phos- transactivating target genes,33 identifying another mecha- phorylate downstream targets, such as CREM (cAMP re- nism by which protein-protein interactions may modulate sponse element modulator), which induces steroidogenic steroidogenic gene transcription. acute regulatory protein (StAR) transcription,15 and hor- Another emerging mechanism by which an extracellu- mone sensitive lipase,16 for the production of free choles- lar signaling factor modulates CYP17 gene expression is terol. It is anticipated that future research will identify in the production of cortisol and dihydroepiandrosterone other proteins whose function in steroidogenesis is regu- in the fetal adrenal, where placental corticotropin-releas- lated by PKA-catalyzed phosphorylation. ing hormone (CRH) signaling induces the mRNA expres- We have shown that ACTH rapidly activates the synthe- sion of several steroidogenic genes, including CYP17, and sis and secretion of the bioactive sphingolipid sphingosine- directly stimulates hormone secretion.34,35 Interestingly, 1-phosphate (S1P).17,18 S1P is then secreted into the extra- the stimulatory effects of CRH on cortisol production in cellular space where it binds to members of the S1P family human fetal adrenal cells were found to be additive with of GPCRs, ultimately resulting in CYP17 transcription and ACTH.34 cortisol production.17,18 Since we have recently identified another sphingolipid, sphingosine, as an endogenous an- tagonist of the nuclear receptor steroidogenic factor-1 (SF- 3. Transcription Factors 1, NR5A1, Ad4BP),19 it is probable that ACTH also in- creases the transactivation potential of SF-1 by promoting Seminal work by the Miller and Waterman laboratories dissociation of sphingosine and rapid conversion to S1P. on the human and bovine CYP17 promoters, established ACTH also rapidly and transiently activates salt-inducible the role of trophic hormone-activated transcription in me- kinase 1, which results in translocation of the enzyme from diating increased steroid hormone output. The stimulatory the nucleus to the cytoplasm where it represses the tran- actions of ACTH and cAMP on steroidogenic gene tran- scription of steroidogenic enzymes,20–23 thereby providing scription were initially demonstrated using primary cul- a mechanism by which adrenocortical cells fine-tune the tures of bovine adrenal cells.36 Although an increase in kinetics of hormone output. mRNA expression supported a role for transcriptional ac- Activation of growth factor signaling pathways such as tivation in maintaining steroidogenic capacity, studies us- the mitogen-activated kinase (MAPK) cascade modulates ing nuclear-run on assays confirmed that gene transcrip- CYP17 gene expression.24–28 Both epidermal growth fac- tion is a prerequisite for cortisol secretion.37 Because bin- tor and basic fibroblast growth factor, probably by activat- ding of ACTH to the melanocortin 2 receptor activates ing the MAPK pathway, suppress CYP17 mRNA expres- adenylyl cyclase and increases intracellular cAMP, it was sion in H295R cells.26 Src kinase, another effector in originally hypothesized that the cAMP response element growth factor signaling, modulates CYP17 mRNA ex- binding protein (CREB) transcription factor mediated the pression and controls adrenal androgen biosynthesis in induction of steroidogenic gene expression. However, un- H295R cells.29 The phorbol ester TPA (12-O-tetrade- like the rapid induction of transcription observed for other canoyl-phorbol-13 acetate), which activates protein ki- CREB targets such as the immediate early genes c-Fos nase C, represses CYP17 mRNA expression in mouse ad- and Jun-B,38,39 the stimulatory actions of cAMP on renal.28 Interestingly, recent studies have found that the steroidogenic gene expression was delayed and took thiazolidinedione and peroxisome proliferator activated hours when compared to cAMP-evoked changes in the ex- receptor-γ (PPARγ) agonist pioglitazone suppresses the pression of immediate early genes.37,40 Moreover, in con- expression of CYP17 via a PPARγ-independent and trast to other CREB targets, increased steroid hydroxylase MAPK-dependent mechanism in the H295R cell line.30 gene expression was cycloheximide-sensitive,41 indicating Another
Load more

Recommended publications
  • A Matter of Degree We Ask Experts What Steers So Many Black Scientists Toward Earning a Master’S Before a Ph.D
    Vol. 19 / No. 2 / February 2020 THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY A matter of degree We ask experts what steers so many black scientists toward earning a master’s before a Ph.D. Don’t wait a lifetime for a decision. C. elegans daf-2 mutants can live up to 40 days. JBC takes only 17 days on average to reach a fi rst decision about your paper. Learn more about fast, rigorous review at jbc.org. www.jbc.org NEWS FEATURES PERSPECTIVES 2 24 52 EDITOR’S NOTE A MATTER OF DEGREE A BEGINNER’S GUIDE TO MINORITY Picking up the slack What steers so many black scientists toward PROFESSOR HIRES 3 earning a master’s before a Ph.D.? NEWS FROM THE HILL 34 Acting to protect research integrity MEYERHOFF SCHOLARS A model for increasing diversity in STEM ANNUAL 4 MEETING MEMBER UPDATE 36 INCLUSIVE EXCELLENCE 7 36 A goal of lasting change NEWS 39 Program at Northeastern aims to fix the Honoring undergrads who promote diversity institution 8 40 RETROSPECTIVE FOR VULNERABLE POPULATIONS, Kensal E. van Holde (1928 – 2019) THE THORNY ETHICS OF GENETIC DATA COLLECTION 10 44 RESEARCH SPOTLIGHT JBC/TABOR AWARDS Understanding how arsenic changes 44 chromatin and causes cancer Award winners to speak at annual 13 24 meeting 45 NEWS Lavrsen finds endless possibilities Don’t wait a lifetime for a decision. Nan-Shan Chang has made WWOX in PTMs his life’s work 46 Varghese roams from forests to C. elegans daf-2 mutants can live up to 40 days.
    [Show full text]
  • Medical Center
    VanderbiltUniversityMedicalCenter Medical Center School of Medicine School of Nursing Hospital and Clinic Vanderbilt University 2002/2003 Containing general information and courses of study for the 2002/2003 session corrected to 1 July 2002 Nashville The University reserves the right, through its established procedures, to modify the require- ments for admission and graduation and to change other rules, regulations, and provisions, including those stated in this bulletin and other publications, and to refuse admission to any student, or to require the withdrawal of a student if it is determined to be in the interest of the student or the University. All students, full- or part-time, who are enrolled in Vanderbilt courses are subject to the same policies. Policies concerning non-curricular matters and concerning withdrawal for medical or emo- tional reasons can be found in the Student Handbook. EQUAL OPPORTUNITY In compliance with federal law, including the provisions of Title IX of the Education Amend- ments of 1972, Sections 503 and 504 of the Rehabilitation Act of 1973, and the Americans with Disabilities Act of 1990, Vanderbilt University does not discriminate on the basis of race, sex, religion, color, national or ethnic origin, age, disability, or military service in its administration of educational policies, programs, or activities; its admissions policies; scholarship and loan programs; athletic or other University-administered programs; or employment. In addition, the University does not discriminate on the basis of sexual orien- tation consistent with University non-discrimination policy. Inquiries or complaints should be directed to the Opportunity Development Officer, Baker Building, VU Station B #351809 Nashville, Tennessee 37235-1809.
    [Show full text]
  • The Member Magazine of the American Society for Biochemistry and Molecular Biology
    Vol. 14 / No. 3 / March 2015 THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY CONTENTS NEWS FEATURES PERSPECTIVES 2 14 50 PRESIDENT’S MESSAGE GIVING PARASITES THEIR DUE COORDINATES Conscience of commitment Chasing the North American Dream 20 4 STEAM 52 NEWS FROM THE HILL When our DNA is fair game CAREER INSIGHTS Gene-editing summit A Q&A with Clemencia Rojas 22 5 ANNUAL MEETING POINTERS 14 MEMBER UPDATE 32 8 ANNUAL AWARDS RETROSPECTIVE Marion Sewer (1972 – 2016) 22 10 JOURNAL NEWS 10 Turning on the thyroid 20 11 Using microRNAs to target cancer cells 12 A mouse model for Hajdu–Cheney syndrome 13 One gene, two proteins, one complex 8 32 50 2016 10 Annual Aards MARCH 2016 ASBMB TODAY 1 PRESIDENT’S MESSAGE THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY Conscience OFFICERS COUNCIL MEMBERS Steven McKnight Squire J. Booker of commitment President Karen G. Fleming Gregory Gatto Jr. Natalie Ahn Rachel Green By Steven McKnight President-Elect Susan Marqusee Karen Allen Jared Rutter Secretary Brenda Schulman Michael Summers very four years, my institution work with the American Society for Toni Antalis Treasurer requires that I take a course Biochemistry and Molecular Biol- ASBMB TODAY EDITORIAL ADVISORY BOARD E and exam regarding conicts ogy, I can help organize and attend EX-OFFICIO MEMBERS Charles Brenner of interest. Past courses have focused meetings, I can give lectures at other Squire Booker Chair primarily on nancial conicts of institutions, I can help found biotech- Wei Yang Michael Bradley Co-chairs, 2016 Annual Floyd “Ski” Chilton interest, but the course and test I took nology companies, and on and on — Meeting Program Cristy Gelling this past month had a new category so long as the activities have legitimate Committee Peter J.
    [Show full text]
  • The Pharmacologist Vol. 54
    Vol. 54 Number 3 2012 The Pharmacologist September ASPET Annual Mee ng at Experimental Biology 2013 Joint mee ng with the Bri sh Pharmacological Society; guest socie es include the Canadian Society for Pharmacology and Therapeu cs & the Behavioral Pharmacology Society Saturday, April 20 - Wednesday, April 24 Skyline from Boston Harbor Paul Revere Statue Fenway Park In this issue: Message from new ASPET President, John Lazo Informa on for ASPET Annual Mee ng at EB 2013 ASPET Membership Survey Results New ASPET Commi ee & Division Lists Congress Returns, Mulls NIH Funding MAPS Annual Mee ng Program Informa on Great Lakes Chapter Mee ng Abstracts Customs House Bunker Hill Monument The Pharmacologist 137 Volume 54 Number 3, 2012 The Pharmacologist is published and distributed by the American Society for Pharmacology and Experimental Contents Therapeu cs. Message from the President 139 EDITOR Gary Axelrod EDITORIAL ADVISORY BOARD ASPET Annual Mee ng at EB 2013 Stephen M. Lanier, PhD Charles P. France, PhD Important Dates 141 Kenneth E. Thummel, PhD COUNCIL Preliminary Program 141 President John S. Lazo, PhD Annual Mee ng News 153 President-Elect Richard R. Neubig, MD, PhD 4th GPCR Colloquium: April 24 - 25, 2013 154 Past President Lynn Wecker, PhD 2012 Annual Membership Survey Results 156 Secretary/Treasurer Edward T. Morgan, PhD New ASPET Commi ee Lists 158 Secretary/Treasurer-Elect Sandra P. Welch, PhD ASPET Commi ee Reorganiza on 160 Past Secretary/Treasurer Mary E. Vore, PhD Journals 162 Councilors Charles P. France, PhD Science Policy 164 Stephen M. Lanier, PhD Kenneth E. Thummel, PhD Chair, Board of Publica ons Trustees Integra ve and Organ System Sciences 166 James E.
    [Show full text]
  • Chromatin, SF-1, and Ctbp Structural and Post-Translational Modifications Induced by ACTH/Camp Accelerate CYP17 Transcription Rate
    Chromatin, SF-1, and CtBP Structural and Post-Translational Modifications Induced by ACTH/cAMP Accelerate CYP17 Transcription Rate A Dissertation Presented to The Academic Faculty By Eric B. Dammer In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in Applied Biology Georgia Institute of Technology December 2008 Chromatin, SF-1, and CtBP Structural and Post-Translational Modifications Induced by ACTH/cAMP Accelerate CYP17 Transcription Rate Approved by: Dr. Marion B. Sewer, Advisor School of Biology Georgia Institute of Technology Dr. Kirill S. Lobachev Dr. Donald F. Doyle School of Biology School of Chemistry and Biochemistry Georgia Institute of Technology Georgia Institute of Technology Dr. Alfred H. Merrill, Jr. Dr. Edward T. Morgan School of Biology Department of Pharmacology Georgia Institute of Technology Emory University History is merely a list of surprises. It can only prepare us to be surprised yet again. -Kurt Vonnegut For Kate and Jeran, and Dad- ACKNOWLEDGEMENTS This work would not have been possible without the support and mentoring of my advisor, Dr. Marion Sewer. The amount of trust she extends and effort she expends on behalf of each of her students makes a tremendous difference not only in the life of each of us, but also in the lives we each have been enabled to touch through our continued efforts after our paths go separate ways. The environment in which scientific exchange occurs has been indispensible for my work to proceed; in particular, I am grateful for the collegial atmosphere of sharing and constructive interaction with fellow lab members, including Aarti Urs, Tuba Ozbay, Adam Leon, Anne Rowan, Dr.
    [Show full text]
  • Frank B. Furnari
    CURRIULUM VITAE Frank B. Furnari Work Address: Ludwig Institute for Cancer Research & University of California, San Diego CMM-E, Room 3053 9500 Gilman Drive La Jolla, CA 92093-0660 Phone: (858) 534-7809 (lab), -7819 (office) Fax: (858) 534-7750 e-mail: [email protected] Date and Place of Birth: May 30, 1964, Queens, New York Education: B.A. awarded: May, 1985 in Biology, Hofstra University, Hempstead, New York Ph.D. awarded: January, 1993 in Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina Professional History: 1987-1993: Graduate student, Microbiology and Immunology, University of North Carolina: Chapel Hill, NC. 2/93-7/00: Postdoctoral fellow, Ludwig Institute for Cancer Research & University of California, San Diego; La Jolla, CA. 8/00-4/07: Assistant Investigator and Head of the Section of Human Carcinogenesis: Ludwig Institute for Cancer Research-San Diego 4/07-11/11: Associate Investigator and Head of the Section of Human Carcinogenesis: Ludwig Institute for Cancer Research-San Diego 11/11-6/15: Senior Investigator and Head of the Section of Human Carcinogenesis: Ludwig Institute for Cancer Research-San Diego 6/15-12/15: Senior Investigator and Head Laboratory of Tumor Biology: Ludwig Institute for Cancer Research-San Diego 1/16-present: Member and Head Laboratory of Tumor Biology: Ludwig Institute for Cancer Research-San Diego 7/01-6/07: Assistant Adjunct Professor, UCSD Department of Medicine 7/07-10/11: Associate Adjunct Professor, UCSD Department of Medicine 3/01-9/05: Associate Member,
    [Show full text]
  • Personal Information Professional Summary
    Personal Information Full Name: L. Ashley Cowart, Ph.D. Title: Professor, Director, Lipidomics Core Facility, Research Health Scientist Business Name: Virginia Commonwealth University Business Address: 1101 E. Marshall St., Sanger Hall 2-016A, Richmond, VA 23219 Phone: 804-827--791 Email: [email protected] Languages Spoken: English Professional Summary Primary Departmental Specialization Area/Field Lipid metabolism, signaling, and biology in the context of diabetes and related metabolic disorders Areas of Expertise and Interest lipid signaling sphingolipids ceramide sphingosine-1-phosphate enzyme kinetics membranes protein structure diabetes obesity non-alcoholic fatty liver disease diabetic cardiomyopathy adipose tissue adipogenesis insulin resistance obesity lipidomics Cowart, Lauren A. 1 of 21 lipid metabolism Education Post Graduate Postdoctoral Fellowship, Medical University of South Carolina, Charleston, SC, Biochemistry and Molecular Biology 08/2001 - 05/2005 Graduate Vanderbilt University, Nashville, TN, NOVEL PATHWAYS OF CYTOCHROME P450- MEDIATED ARACHIDONIC ACID BIOACTIVATION, Jorge H. Capdevila. 08/1995 - 12/2001 Undergraduate Furman University, Greenville, SC, Biology, B.S., 1995, 08/1991 - 05/1995 Academic Appointment History Professor, tenure track, Virginia Commonwealth University College of Medicine 11/2017 - Present Associate Professor with tenure, Medical University of South Carolina College of Medicine 01/2017 - 10/2017 Associate Professor, tenure track, Medical University of South Carolina College of Medicine 07/2014 - 12/2016 Assistant Professor, tenure track, Medical University of South Carolina College of Medicine 06/2009 - 06/2014 Assistant Professor, research track, Medical University of South Carolina College of Medicine 07/2005 - 05/2009 Employment History Research Health Scientist, McGuire Veterans Affairs Medical Center 11/2017 - Present Director, Lipidomics Shared Resource Facility, Virginia Commonwealth University College of Medicine 02/2018 (in progress) Cowart, Lauren A.
    [Show full text]
  • Regulation of Ceramide and Its Metabolites
    REGULATION OF CERAMIDE AND ITS METABOLITES: BIOSYNTHESIS & IN SITU SPHINGOLIPID ANALYSIS A Dissertation Presented to The Academic Faculty by Ying Liu In Partial Fulfillment of the Requirements for the Degree PH.D in the School of Biology Georgia Institute of Technology May/2010 REGULATION OF CERAMIDE AND ITS METABOLITES: BIOSYNTHESIS & IN SITU SPHINGOLIPID ANALYSIS Approved by Dr. Alfred Merrill, Advisor Dr. Julian Kubanek School of Biology School of Biology Georgia Institute of Technology Georgia Institute of Technology Dr. Marion Sewer Dr. Harish Radhakrishna Skaggs School of Pharmacy & Strategic Research Department Pharmaceutical Sciences The Coca-Cola Company University of California Dr. Paula M. Vertino Winship Cancer Institute Emory University Date Approved: Dec 14 th , 2010 ii To my familiy iii ACKNOWLEDGEMENTS First of all, I would like to thank Dr. Alfred Merrill, my advisor, for giving me the opportunity to join his research group and explore the exciting research world of sphingolipids. Without his encouragement, support and guidance through my whole graduate studies here at Georgia Tech, I could not have achieved the goal. I am so grateful to my thesis committee members: Dr. Julia Kubanek, Dr. Marion Sewer, Dr. Paula M. Vertino, Dr. Harish Radhakrishna, for their time and good advices. I want to express my appreciation to Dr. Yanfeng Chen and Samuel Kelly, for their valuable guidance and insightful comments in the field of mass spectrometry. Special thanks to Dr. Cameron Sullards, David Bostwick in mass spectrometry facilities. I would like to thank Dr. Martina Leipelt and Dr. Qiong Peng for their generous help in molecular biology. I am grateful to Dr.
    [Show full text]
  • [Thesis Title Goes Here]
    APPLICATION OF BIOINFORMATICS IN STUDIES OF SPHINGOLIPID BIOSYNTHESIS A Dessertation Presented to The Academic Faculty by Amin Altaf Momin In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the School of Biology, College of sciences Georgia Institute of Technology August 2010 APPLICATION OF BIOINFORMATICS IN STUDIES OF SPHINGOLIPID BIOSYNTHESIS Approved by: Dr. Alfred H Merrill Jr, Advisor Dr. Stephen C Harvey School of Biology School of Biology Georgia Institute of Technology Georgia Institute of Technology Dr Cameron Sullards Dr. Marion B. Sewer School of Chemistry and Biochemistry School of Pharmacy and Georgia Institute of Technology Pharmaceutical Sciences University of California, San Diego Dr I King Jordan School of Biology Georgia Institute of Technology Date Approved: 05/14/2010 This thesis is dedicated to my parents iii ACKNOWLEDGEMENTS I wish to thanks my Advisor Dr Alfred Merrill for all his kind advice and support during my graduate study. His encouragement and insight has been instrumental in shaping studies and overcoming challenging during my project. I would also like to think my committee members Dr Marion Sewer, Dr King Jordan, Dr Cameron Sullards, Dr Steve Harvey and a previous member Dr John Cairney for their valuable advice and constructive feedback during my dissertation. All this work wouldn’t be possible without the support of all my co-workers in the Merrill lab including Samuel Kelly, Chris Haynes, Hyejung Park, Kacee Sim, Kristin Jones, Jeremy Allegood, Jia Wei, Rebecca Shaner, Ying Liu, Martina Liepelt and Brent Portz. I am especially thankful to Elaine Wang for her advice and support during all these years in graduate school.
    [Show full text]
  • Modulating the Functional Contributions of C-Myc to the Human Endothelial Cell Cyclic Strain Response
    MODULATING THE FUNCTIONAL CONTRIBUTIONS OF C-MYC TO THE HUMAN ENDOTHELIAL CELL CYCLIC STRAIN RESPONSE A Dissertation Presented to The Academic Faculty By Nicole Elizabeth Hurley In Partial Fulfillment Of the Requirements for the Degree Doctor of Philosophy in Bioengineering Georgia Institute of Technology December, 2007 MODULATING THE FUNCTIONAL CONTRIBUTIONS OF C-MYC TO THE HUMAN ENDOTHELIAL CELL CYCLIC STRAIN RESPONSE Approved by: Dr. Larry McIntire, Advisor Dr. Todd McDevitt Wallace H. Coulter Department of Wallace H. Coulter Department of Biomedical Engineering Biomedical Engineering Georgia Institute of Technology and Georgia Institute of Technology and Emory University School of Medicine Emory University School of Medicine Dr. Suzanne Eskin Dr. Marion Sewer Wallace H. Coulter Department of School of Biology Biomedical Engineering Georgia Institute of Technology Georgia Institute of Technology and Emory University School of Medicine Dr. Raymond Vito The George W. Woodruff School of Mechanical Engineering Georgia Institute of Technology Date approved: October 30, 2007 To my family, with love, for always encouraging me, believing in me, and for reminding me what really matters. iii ACKNOWLEDGEMENTS I would like to express my deep gratitude to the many people who have given me invaluable support for this work and my graduate studies. I would like to thank my advisors at Georgia Tech, Dr. Larry V. McIntire and Dr. Suzanne G. Eskin, for their continued knowledge, guidance, support and patient direction. Thank you to Dr. Zorina Galis for giving me support, generosity and an educating spirit during my work at Emory University. In addition, I appreciate the valuable input and guidance of the rest of my thesis committee, Dr.
    [Show full text]
  • American Society for Biochemistry and Molecular Biology
    Vol. 12 No. 8 September 2013 American Society for Biochemistry and Molecular Biology contents SEPTEMBER 2013 In our cover story, science writer Rajendrani news Mukhopadhyay talks to frequent-flyers who are 2 President’s Message maintaining research Solving the insoluble (and watching them dance) programs in different parts of the world. 14 5 Member Update An open letter to our readers who have something to say 6 News from the Hill but need a place (and maybe even permission) to say it Will this time be any different? 7 Herbert Tabor Young Dear Reader, Investigator awards This is your magazine. Seriously, it is. You support it when you renew your ASBMB dues, share its contents with 8 Retrospective your friends and colleagues, crack it open on the train and even when you use it as a coaster for your coffee mug. Christian de Duve (1917 – 2013) In the second to last installment of our It’s yours. series, H. Jane Dyson writes about her essay winding career path. 12 Over the past two years, we’ve worked hard to get more of *you* in these pages. We’ve asked for your science- 10 Jack of a few trades, inspired poems (thanks for humoring me), your unique perspectives (keep ’em coming) and, most recently, your Master of Science inspiring stories of failure and triumph (the “Derailed but Undeterred” series). Your contributions have trans- formed this magazine into one with greater depth, unique storytelling and diversity of ideas. features For our next essay series, to be published in 2014, we want your letters.
    [Show full text]
  • Androgen-Independent Prostate Cancer Cells Acquire the Complete Steroidogenic Potential of Synthesizing Testosterone from Cholesterol
    University of Nebraska Medical Center DigitalCommons@UNMC Journal Articles: Biochemistry & Molecular Biology Biochemistry & Molecular Biology 11-25-2008 Androgen-independent prostate cancer cells acquire the complete steroidogenic potential of synthesizing testosterone from cholesterol. Paulette R. Dillard Clark Atlanta University Ming-Fong Lin University of Nebraska Medical Center, [email protected] Shafiq A. Khan Clark Atlanta University Follow this and additional works at: https://digitalcommons.unmc.edu/com_bio_articles Part of the Medical Biochemistry Commons, and the Medical Molecular Biology Commons Recommended Citation Dillard, Paulette R.; Lin, Ming-Fong; and Khan, Shafiq A., Andr" ogen-independent prostate cancer cells acquire the complete steroidogenic potential of synthesizing testosterone from cholesterol." (2008). Journal Articles: Biochemistry & Molecular Biology. 35. https://digitalcommons.unmc.edu/com_bio_articles/35 This Article is brought to you for free and open access by the Biochemistry & Molecular Biology at DigitalCommons@UNMC. It has been accepted for inclusion in Journal Articles: Biochemistry & Molecular Biology by an authorized administrator of DigitalCommons@UNMC. For more information, please contact [email protected]. NIH Public Access Author Manuscript Mol Cell Endocrinol . Author manuscript; available in PMC 2010 January 5. NIH-PA Author NIH-PA ManuscriptPublishedAuthor NIH-PA Manuscript in final editedAuthor NIH-PA Manu form as: Mol Cell Endocrinol . 2008 November 25; 295(1-2): 115–120. doi:10.1016/j.mce.2008.08.013.
    [Show full text]