Abstract

This proposal is to continue studies on the molecular properties of two members of the heat shock factor (HSF) family and to identify the upstream signals involved in the cellular stress response. The inducible transcription of heat shock genes is mediated by the activities of a family of HSFs. HSF1 and HSF2 are the foci of this proposal. HSF1 is the major stress-responsive transcription factor activated by heat shock, oxidative stress, heavy metals, and other forms of physiological stress, whereas HSF2 is a closely related factor whose activities are activated by distinct conditions including early murine development and differentiation. The goals of the proposed studies are to understand how the activities of a family of heat shock transcription factors (HSFs) are regulated in response to diverse environmental and physiological conditions that modulate the transcription of genes encoding heat shock proteins and molecular chaperons.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM038109-13
Application #
2900647
Study Section
Molecular Biology Study Section (MBY)
Program Officer
Anderson, James J
Project Start
1987-04-01
Project End
2000-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
13
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Northwestern University at Chicago
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60201

  Publications

Ciryam, Prajwal; Kundra, Rishika; Freer, Rosie et al. (2016) A transcriptional signature of Alzheimer's disease is associated with a metastable subproteome at risk for aggregation. Proc Natl Acad Sci U S A 113:4753-8
Nussbaum-Krammer, Carmen I; Neto, Mário F; Brielmann, Renée M et al. (2015) Investigating the spreading and toxicity of prion-like proteins using the metazoan model organism C. elegans. J Vis Exp :52321
Ciryam, Prajwal; Kundra, Rishika; Morimoto, Richard I et al. (2015) Supersaturation is a major driving force for protein aggregation in neurodegenerative diseases. Trends Pharmacol Sci 36:72-7
Labbadia, Johnathan; Morimoto, Richard I (2015) The biology of proteostasis in aging and disease. Annu Rev Biochem 84:435-64
Tatum, Marcus C; Ooi, Felicia K; Chikka, Madhusudana Rao et al. (2015) Neuronal serotonin release triggers the heat shock response in C. elegans in the absence of temperature increase. Curr Biol 25:163-174
Kirstein, Janine; Morito, Daisuke; Kakihana, Taichi et al. (2015) Proteotoxic stress and ageing triggers the loss of redox homeostasis across cellular compartments. EMBO J 34:2334-49
Nillegoda, Nadinath B; Kirstein, Janine; Szlachcic, Anna et al. (2015) Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation. Nature 524:247-51
Brandvold, Kristoffer R; Morimoto, Richard I (2015) The Chemical Biology of Molecular Chaperones--Implications for Modulation of Proteostasis. J Mol Biol 427:2931-47
Labbadia, Johnathan; Morimoto, Richard I (2015) Repression of the Heat Shock Response Is a Programmed Event at the Onset of Reproduction. Mol Cell 59:639-50
Walther, Dirk M; Kasturi, Prasad; Zheng, Min et al. (2015) Widespread Proteome Remodeling and Aggregation in Aging C. elegans. Cell 161:919-32

Showing the most recent 10 out of 75 publications