Article
Multidisciplinary Sciences
Roger S. Smith, Seesha R. Takagishi, David R. Amici, Kyle Metz, Sitaram Gayatri, Milad J. Alasady, Yaqi Wu, Sonia Brockway, Stephanie L. Taiberg, Natalia Khalatyan, Mikko Taipale, Sandro Santagata, Luke Whitesell, Susan Lindquist, Jeffrey N. Savas, Marc L. Mendillo
Summary: Heat shock factor 1 (HSF1) plays a crucial role in the heat shock response and tumorigenesis. This study reveals that HSF2 interacts with HSF1 in various types of cancer. HSF1 and HSF2 have similar chromatin occupancy and regulate a common set of genes, including HSPs and noncanonical transcriptional targets critical for supporting malignancy.
Article
Cell Biology
Mooud Amirkavei, Flavia Plastino, Anders Kvanta, Kai Kaarniranta, Helder Andre, Ari Koskelainen
Summary: Cells have stress-response pathways to cope with stress factors for homeostasis maintenance; low doses of stress may be beneficial; HHS was found to enhance autophagy gene expression and activation through HSF1.
Review
Oncology
Anna M. Cyran, Anatoly Zhitkovich
Summary: The fitness of cells depends on the maintenance of protein homeostasis, which is achieved through the cooperative activities of protein chaperones and proteolytic machinery. In response to protein-damaging conditions, cells activate the heat-shock response (HSR) by upregulating a group of chaperones known as heat shock proteins (HSPs). Cancer cells, which experience high levels of proteotoxic stress, often upregulate major components of HSR, including HSF1 and individual HSPs. Elevated levels of HSPs and HSF1 are associated with drug resistance and poor clinical outcomes in various types of cancer. Targeting protein quality controls represents a promising approach for the treatment of human malignancies, as it can enhance the efficacy of standard and targeted chemotherapy as well as immune checkpoint inhibitors. In cancers with specific dependencies, HSR components can serve as alternative targets to oncogenic drivers that are difficult to drug.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Marie Pariollaud, Lara H. Ibrahim, Emanuel Irizarry, Rebecca M. Mello, Alanna B. Chan, Brian J. Altman, Reuben J. Shaw, Michael J. Bollong, R. Luke Wiseman, Katja A. Lamia
Summary: Chronic circadian disruption increases tumor burden in a mouse model of lung cancer through enhanced expression and nuclear accumulation of HSF1.
Review
Biochemistry & Molecular Biology
Tahir Muhammad, Jian Li
Summary: Protein homeostasis is crucial for cellular function and organismal health, especially in germ cells where proteome integrity is essential for genome stability. The heat shock factor 1 (HSF1) and insulin/insulin-like growth factor-1 (IGF-1) signaling play important roles in regulating proteostasis during germline development. This review focuses on the roles of HSF1 and IIS in maintaining germline proteostasis and their implications on gamete quality control under stress and aging conditions.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Multidisciplinary Sciences
Mitsuaki Fujimoto, Ryosuke Takii, Masaki Matsumoto, Mariko Okada, Keiich I. Nakayama, Ryuichiro Nakato, Katsunori Fujiki, Katsuhiko Shirahige, Akira Nakai
Summary: The study shows that phosphorylation of HSF1 during heat shock recruits histone acetyltransferases and histone acetylation reader proteins TRIM33 and TRIM24 to the HSP72 promoter, leading to histone H2B mono-ubiquitination, promoting the establishment of an active chromatin status, and affecting melanoma cell proliferation.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Mingyuan Wang, Jiang Zou, Jinjin Wang, Meidong Liu, Ke Liu, Nian Wang, Kangkai Wang
Summary: This study investigated the protective effect of metformin on myocardial tissue and identified HSF1 as a key target. Metformin stimulated the activation of HSF1, which up-regulated AMPKa2 and activated the downstream AMPK/mTOR signaling pathway. HSF1 exhibited a higher affinity for metformin than AMPK, suggesting that it may be a more sensitive target.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Medicine, Research & Experimental
Xia Gao, Keyin Zhang, Haiyan Zhou, Lucas Zellmer, Chengfu Yuan, Hai Huang, Dezhong Joshua Liao
Summary: This study found that in high temperature conditions, heat shock proteins and associated genes not only increase their expression, but also use multiple mechanisms to produce various RNA transcripts and protein isoforms.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Editorial Material
Biochemistry & Molecular Biology
Thomas MacVicar, Thomas Langer
Summary: Mechanical forces influence extracellular matrix stiffness, which in turn alters mitochondrial shape and function, enhancing resistance to oxidative stress and promoting cell survival.
Article
Biochemistry & Molecular Biology
Pratibha Srivastava, Ryosuke Takii, Mariko Okada, Mitsuaki Fujimoto, Akira Nakai
Summary: The CKM module plays a crucial role in heat-shock transcription, promoting HSP70 expression through the kinase activity of CDK8 and CDK19, and maintaining proteostasis capacity to protect cells against proteotoxic stress.
Article
Biochemistry & Molecular Biology
Eileen T. Burchfiel, Anniina Vihervaara, Michael J. Guertin, Rocio Gomez-Pastor, Dennis J. Thiele
Summary: Studies have identified changes in HSF1 interacting proteins under normal growth and various stress conditions, as well as new HSF1 interacting proteins in a Huntington's disease cell model, showing involvement in cellular functions such as DNA repair and mRNA processing.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Tamara Isermann, Ozge Cicek Sener, Adrian Stender, Luisa Klemke, Nadine Winkler, Albrecht Neesse, Jinyu Li, Florian Wegwitz, Ute M. Moll, Ramona Schulz-Heddergott
Summary: The discovery of the WT P53-HSF1 axis in cancer reveals a mechanism driving p53LOH, where the WT p53 allele suppresses HSF1, preventing mutant p53 stabilization and gain-of-function activities, leading to selective pressure for p53LOH.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Natalia Vydra, Agnieszka Toma-Jonik, Patryk Janus, Katarzyna Mrowiec, Tomasz Stokowy, Magdalena Glowala-Kosinska, Damian Robert Sojka, Magdalena Olbryt, Wieslawa Widlak
Summary: Epithelial-to-mesenchymal transition (EMT) is important for development and wound healing, but can also contribute to organ fibrosis and cancer metastasis. This study suggests that the heat shock transcription factor 1 (HSF1) may be involved in EMT in human mammary epithelial cells, and inhibiting HSF1 could potentially be a treatment for breast cancer.
Article
Oncology
Weikun Qian, Ke Chen, Tao Qin, Ying Xiao, Jie Li, Yangyang Yue, Cancan Zhou, Jiguang Ma, Wanxing Duan, Jianjun Lei, Liang Han, Li Li, Xin Shen, Zheng Wu, Qingyong Ma, Zheng Wang
Summary: In this study, pharmacological inhibition of HSF1 was found to slow pancreatic cancer initiation and suppress pancreatitis-induced formation of pancreatic precancerous lesions. Bioinformatics analysis revealed a close link between HSF1 and the EGFR pathway, with their parallel activation in pancreatic precancerous lesions. Additionally, inhibition of EGFR was shown to suppress pancreatic cancer initiation and HSF1 activation in vivo, indicating a partly HSF1-dependent mechanism of EGFR-mediated pancreatic cancer tumorigenesis.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Cell Biology
Stefan Gabriel, Thomas Czerny, Elisabeth Riegel
Summary: The heat shock factor 1 (HSF1) is a transcription factor that acts as a stress sensor and regulates the heat shock response (HSR). The activation of HSF1 is regulated by stress-specific phosphorylation, although the exact mechanisms are not fully understood. This study investigated the effects of amino acid substitutions on phosphorylation sites of HSF1 and identified a small repressive motif that can suppress the transcriptional output of the HSR.
CELLULAR SIGNALLING
(2023)
Article
Neurosciences
Xiaofeng Gu, Jeffrey Richman, Peter Langfelder, Nan Wang, Shasha Zhang, Monica Banez-Coronel, Huei-Bin Wang, Lucia Yang, Lalini Ramanathan, Linna Deng, Chang Sin Park, Christopher R. Choi, Jeffrey P. Cantle, Fuying Gao, Michelle Gray, Giovanni Coppola, Gillian P. Bates, Laura P. W. Ranum, Steve Horvath, Christopher S. Colwell, X. William Yang
Summary: In this study, a BAC-CAG mouse model was established to investigate the pathogenesis of Huntington's disease, and it was found that the uninterrupted CAG repeat length is significantly correlated with striatal transcriptionopathy, but not with polyglutamine length. Additionally, somatic CAG repeat instability and nuclear mHTT aggregation are best correlated with early-onset pathology and locomotor and sleep deficits.
Article
Clinical Neurology
Sandra Fienko, Christian Landles, Kirupa Sathasivam, Sean J. McAteer, Rebecca E. Milton, Georgina F. Osborne, Edward J. Smith, Samuel T. Jones, Marie K. Bondulich, Emily C. E. Danby, Jemima Phillips, Bridget A. Taxy, Holly B. Kordasiewicz, Gillian P. Bates
Summary: Fienko et al. show that alternative processing of human huntingtin (HTT) mRNA to generate HTT1a occurs in YAC128 mice, which has implications for the design of huntingtin-lowering therapies.
Article
Multidisciplinary Sciences
Karlijne W. Geijtenbeek, Jolien Janzen, Aleksandra E. Bury, Alicia Sanz-Sanz, Ron A. Hoebe, Marie K. Bondulich, Gillian P. Bates, Eric A. J. Reits, Sabine Schipper-Krom
Summary: Huntington's disease, caused by a gene mutation, may be treated by lowering the levels of mutant protein. Research has shown that in affected brain regions, the proteasome separates from PA28αβ, which may be related to disease progression.
Article
Neurosciences
Jenny Lange, Olivia Gillham, Michael Flower, Heather Ging, Simon Eaton, Sneha Kapadia, Andreas Neueder, Michael R. Duchen, Patrizia Ferretti, Sarah J. Tabrizi
Summary: Huntington's Disease is a neurodegenerative disease caused by a genetic mutation. Astrocyte dysfunction, specifically changes in gene expression and metabolic activity, plays a role in the pathogenesis of the disease. Additionally, all Huntington's Disease astrocytes exhibit increased DNA damage and a DNA damage response, suggesting a potential mechanism for their dysfunction.
PROGRESS IN NEUROBIOLOGY
(2023)
Meeting Abstract
Clinical Neurology
Alshaimaa A. B. Abdelmoez, Michael Orth, Andreas Neueder
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Sandra Fienko, Christian Landles, Kirupa Sathasivam, Casandra Gomez-Paredes, Sean McAteer, Rebecca Milton, Georgina F. Osborne, Samuel T. Jones, Jemima M. Phillips, Holly B. Kordasiewicz, Gillian P. Bates
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Franziska Hoschek, Kerstin Kojer, Mirjam Skobowsky, Nathalie Birth, Andreas Neueder, Michael Orth
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Christian Landles, Georgina F. Osborne, Rebecca E. Milton, Alexandre Jean, Stuart McLarnon, Chuangchuang Zhang, Wenzhen Duan, Gillian P. Bates
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Julia Natan, Franziska Hoschek, Andreas Neueder
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Andreas Neueder, Philipp Nitzschner, Ronja Wagner, Julia Hummel, Franziska Hoschek, Maximilian Wagner, Alshaimaa Abdelmoez, Bjoern von Einem, Sarah Tabrizi, Michael Orth
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Aikaterini-Smaragdi Papadopulou, Christian Landles, Edward Smith, Marie Bondulich, Arzo Iqbal, Georgina F. Osborne, David Howland, Andreas Neueder, Gillian P. Bates
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Edward J. Smith, Kirupa Sathasivam, Christian Landles, Georgina F. Osborne, Casandra Gomez-Paredes, Gillian P. Bates
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Bjoern von Einem, Alshaimaa Abdelmoez, Jan Lewerenz, G. Bernhard Landwehrmeyer, Andreas Neueder
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Biotechnology & Applied Microbiology
Andreas Neueder, Kerstin Kojer, Tanja Hering, Daniel J. Lavery, Jian Chen, Nathalie Birth, Jaqueline Hallitsch, Sonja Trautmann, Jennifer Parker, Michael Flower, Huma Sethi, Salman Haider, Jong-Min Lee, Sarah J. Tabrizi, Michael Orth
Summary: This study analyzed transcriptomics and proteomics data from peripheral tissues of HD patients, identifying changes in inflammation, energy metabolism, and extracellular vesicle homeostasis. These biological signatures have the potential to serve as biomarkers in HD clinical trials. Additionally, the generated data and cell lines established from peripheral tissues provide a valuable resource for advancing understanding of HD pathogenesis.