[GRG] Regulating Heat Shock Transcription Factor 1 – Max Planck Institute

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Interplay of Acetyltransferase EP300 and the Proteasome System in
Regulating Heat Shock Transcription Factor 1

Cell, Volume 156, Issue 5, 975-985, 27 February 2014
Copyright © 2014 Elsevier Inc. All rights reserved.
10.1016/j.cell.2014.01.055

Authors

Swasti Raychaudhuri

,

Christian Loew

,

Roman Körner

,

Stefan Pinkert

,

Mirko Theis

,

Manajit Hayer-Hartl

,

Frank Buchholz

,

F. Ulrich Hartl
send emailSee Affiliations

Highlights
•RNAi identifies heat stress response modulators in different
cellular locations
•Chromatin modifiers and nuclear proteasome are critical stress
response regulators
•EP300 acetylates HSF1 and regulates its stability and cellular
level
•The proteasome attenuates the stress response by degrading
activated HSF1

Summary

When exposed to proteotoxic environmental conditions, mammalian
cells activate the cytosolic stress response in order to restore
protein homeostasis. A key feature of this response is the heat
shock transcription factor 1 (HSF1)-dependent expression of
molecular chaperones. Here, we describe the results of an RNA
interference screen in HeLa cells to identify modulators of stress
response induction and attenuation. The modulator proteins are
localized in multiple cellular compartments, with chromatin
modifiers and nuclear protein quality control playing a central
regulatory role. We find that the acetyltransferase, EP300,
controls the cellular level of activatable HSF1. This involves
acetylation of HSF1 at multiple lysines not required for function
and results in stabilization of HSF1 against proteasomal turnover.
Acetylation of functionally critical lysines during stress serves
to fine-tune HSF1 activation. Finally, the nuclear proteasome
system functions in attenuating the stress response by degrading
activated HSF1 in a manner linked with the clearance of misfolded
proteins.

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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