Regulation of Autophagy by the Heat Shock Factor 1-Mediated Stress Response Pathway

2018 ◽  
pp. 167-178
Author(s):  
Yoshihisa Watanabe ◽  
Masaki Tanaka
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1 ◽  
Stress Response Pathway

scholarly journals DYRK2 activates heat shock factor 1 promoting resistance to proteotoxic stress in triplenegative breast cancer

2019 ◽  
Author(s):  
Rita Moreno ◽  
Sourav Banerjee ◽  
Angus W. Jackson ◽  
Jean Quinn ◽  
Gregg Baillie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heat Shock ◽  
Cancer Progression ◽  
Xenograft Model ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1 ◽  
Proteotoxic Stress ◽  
Dual Specificity ◽  
Stress Response Pathway ◽  
Nuclear Stability

SummaryTo survive aneuploidy-induced proteotoxic stress, cancer cells activate the proteotoxic-stress response pathway, which is controlled by heat shock factor 1 (HSF1). This pathway supports cancer initiation, cancer progression and chemoresistance and thus is an attractive target. As developing HSF1 inhibitors is challenging, the identification and targeting of upstream regulators of HSF1 presents a tractable alternative strategy. Here we demonstrate that in triple negative breast cancer (TNBC) cells, the dual-specificity tyrosine-regulated kinase 2 (DYRK2) phosphorylates HSF1, promoting its nuclear stability and transcriptional activity. Thus, DYRK2 depletion reduces HSF1 activity and sensitises TNBC cells to proteotoxic stress. Importantly, in tumours from TNBC patients, DYRK2 levels positively correlate with active HSF1 and associates with poor prognosis, suggesting that DYRK2 could be promoting TNBC. In agreement with this, DYRK2 depletion reduces tumour growth in a TNBC xenograft model. These findings identify DYRK2 as both, a key modulator of the HSF1 transcriptional program, and a potential therapeutic target.

scholarly journals The stress-responsive kinase DYRK2 activates heat shock factor 1 promoting resistance to proteotoxic stress

2020 ◽  
Author(s):  
Rita Moreno ◽  
Sourav Banerjee ◽  
Angus W. Jackson ◽  
Jean Quinn ◽  
Gregg Baillie ◽  
...  
Keyword(s):  
Heat Shock ◽  
Cancer Progression ◽  
Therapeutic Target ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1 ◽  
Proteotoxic Stress ◽  
Dual Specificity ◽  
Stress Response Pathway ◽  
Nuclear Stability ◽  
Attractive Therapeutic Target

AbstractTo survive proteotoxic stress, cancer cells activate the proteotoxic-stress response pathway, which is controlled by the transcription factor heat shock factor 1 (HSF1). This pathway supports cancer initiation, cancer progression and chemoresistance and thus is an attractive therapeutic target. As developing inhibitors against transcriptional regulators, such as HSF1 is challenging, the identification and targeting of upstream regulators of HSF1 present a tractable alternative strategy. Here we demonstrate that in triple-negative breast cancer (TNBC) cells, the dual specificity tyrosine-regulated kinase 2 (DYRK2) phosphorylates HSF1, promoting its nuclear stability and transcriptional activity. DYRK2 depletion reduces HSF1 activity and sensitises TNBC cells to proteotoxic stress. Importantly, in tumours from TNBC patients, DYRK2 levels positively correlate with active HSF1 and associates with poor prognosis, suggesting that DYRK2 could be promoting TNBC. These findings identify DYRK2 as a key modulator of the HSF1 transcriptional programme and a potential therapeutic target.

scholarly journals Physiological Fever Temperature Induces a Protective Stress Response in T Lymphocytes Mediated by Heat Shock Factor-1 (HSF1)

2007 ◽  
Vol 179 (12) ◽  
pp. 8305-8312 ◽  
Author(s):  
Patience Murapa ◽  
Siva Gandhapudi ◽  
Hollie S. Skaggs ◽  
Kevin D. Sarge ◽  
Jerold G. Woodward
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
T Lymphocytes ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1

scholarly journals Heat shock factor 1 is a key regulator of the stress response in Chlamydomonas

2007 ◽  
Vol 52 (2) ◽  
pp. 286-295 ◽  
Author(s):  
Miriam Schulz-Raffelt ◽  
Mukesh Lodha ◽  
Michael Schroda
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1

scholarly journals Receptor-interacting protein 140 as a co-repressor of Heat Shock Factor 1 regulates neuronal stress response

2017 ◽  
Vol 8 (12) ◽  
Author(s):  
Yu-Lung Lin ◽  
Hong-Chieh Tsai ◽  
Pei-Yao Liu ◽  
Michael Benneyworth ◽  
Li-Na Wei
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1 ◽  
Interacting Protein ◽  
Neuronal Stress

scholarly journals Protein level variability determines phenotypic heterogeneity in proteotoxic stress response

2019 ◽  
Author(s):  
Marie Guilbert ◽  
François Anquez ◽  
Alexandra Pruvost ◽  
Quentin Thommen ◽  
Emmanuel Courtade
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Response ◽  
Phenotypic Variability ◽  
Heat Shock Factor ◽  
Phenotypic Heterogeneity ◽  
Expression Level ◽  
Heat Shock Factor 1 ◽  
Response Network ◽  
Shock Response

AbstractCell-to-cell variability in stress response is a bottleneck for the construction of accurate and predictive models that could guide clinical diagnosis and treatment of diseases as for instance cancers. Indeed such phenotypic heterogeneity can lead to fractional killing and persistence of a subpopulation of cells resistant to a given treatment. The heat shock response network plays a major role in protecting the proteome against several types of injuries. We combine high-throughput measurements and mathematical modeling to unveil the molecular origin of the phenotypic variability in the heat shock response network. Although the mean response coincides with known biochemical measurements, we found a surprisingly broad diversity in single cell dynamics with a continuum of response amplitudes and temporal shapes for several stimuli strengths. We theoretically predict that the broad phenotypic heterogeneity is due to network ultrasensitivity together with variations in the expression level of chaperons controlled by heat shock factor 1. We experimentally confirm this prediction by mapping the response amplitude to concentrations chaperons and heat shock factor 1 expression level.

scholarly journals A physiological role of heat shock factor 1‐related stress response in the regrowth of atrophied soleus muscle in mice

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Katsumasa Goto ◽  
Yoshitaka Ohno ◽  
Ayumi Goto ◽  
Ayane Nakamura ◽  
Akira Nakai ◽  
...  
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Soleus Muscle ◽  
Physiological Role ◽  
Heat Shock Factor ◽  
Heat Shock Factor 1 ◽  
Related Stress
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