Targeted Deletion of Hsf1, 2, and 4 Genes in Mice

Jin, Xin; Eroglu, Binnur; Moskophidis, Demetrius; Mivechi, Nahid F.

doi:10.1007/978-1-4939-7477-1_1

Cited by 14 publications

(11 citation statements)

References 40 publications

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“…Unlike a single HSF in invertebrates, six HSFs have been found in mammals (HSF1, HSF2, HSF3, HSF4, HSFX, and HSFY), and plants are known to express more than thirty different HSFs (for comprehensive reviews see [2,12,13]). Among the five human HSFs, the functions of HSF1, HSF2, and HSF4 have been most extensively studied [1,14,15]. Since the structural domains in HSF proteins have been described in great detail in a recent review [2], they are only briefly summarized here.…”

Section: Domain Structure In Hsfsmentioning

confidence: 99%

“…Studies using HSF-null mice have made it possible to further identify the physiological and developmental processes in which HSF1, HSF2, and HSF4 are involved. All HSF-null mice are viable but display distinct phenotypes, such as abnormalities in sensory organs and the brain, while others have similar phenotypes, such as impaired fertility, for details, see below [14,55,56]. Of note, HSF-null mice are regarded as a representative model, since murine HSFs display more than 84% identical amino acid sequence to human HSFs.…”

Section: Hsfs As Developmental Factorsmentioning

confidence: 99%

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Molecular Mechanisms of Heat Shock Factors in Cancer

Puustinen,

Sistonen

2020

Cells

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Malignant transformation is accompanied by alterations in the key cellular pathways that regulate development, metabolism, proliferation and motility as well as stress resilience. The members of the transcription factor family, called heat shock factors (HSFs), have been shown to play important roles in all of these biological processes, and in the past decade it has become evident that their activities are rewired during tumorigenesis. This review focuses on the expression patterns and functions of HSF1, HSF2, and HSF4 in specific cancer types, highlighting the mechanisms by which the regulatory functions of these transcription factors are modulated. Recently developed therapeutic approaches that target HSFs are also discussed.

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Section: Domain Structure In Hsfsmentioning

confidence: 99%

Section: Hsfs As Developmental Factorsmentioning

confidence: 99%

Molecular Mechanisms of Heat Shock Factors in Cancer

Puustinen,

Sistonen

2020

Cells

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“…More recently, it has been shown that HSF1 is abundant in the nuclei of mammary tumor cells in clinical biopsy samples, indicating constitutive activation of the heat shock response in cancer [38]. Perhaps most significantly, it has been shown that knockout of HSF1 in mouse tumor models, including p53-deficient or Her2-overexpressing spontaneous cancer, severely curtails tumor growth [13,[45][46][47][62][63][64]. These studies provide strong evidence for an important causal and essential role for the factor in tumorigenesis.…”

Section: Roles For Hsf1 In Cellular Processes Associated With Transfomentioning

confidence: 90%

“…The importance of the HSR is underscored by the existence of more than five HSF paralogs in humans [13], although only HSF1, HSF2, and HSF4 have been reported in the cancer literature. HSF2 influences neurodevelopment and is able to amplify the HSR in collaboration with HSF1 [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…HSF1 is therefore generally considered the most robust regulator of HSP expression and the major mediator of increased HSPs in cancer. The majority of the available information related to HSP expression from both the stress response and cancer fields involves HSF1, and we have therefore concentrated on this principal transcription factor [13].…”

Section: Introductionmentioning

confidence: 99%

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HSF1: Primary Factor in Molecular Chaperone Expression and a Major Contributor to Cancer Morbidity

Prince

Lang

Guerrero-Gimenez

et al. 2020

Cells

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Heat shock factor 1 (HSF1) is the primary component for initiation of the powerful heat shock response (HSR) in eukaryotes. The HSR is an evolutionarily conserved mechanism for responding to proteotoxic stress and involves the rapid expression of heat shock protein (HSP) molecular chaperones that promote cell viability by facilitating proteostasis. HSF1 activity is amplified in many tumor contexts in a manner that resembles a chronic state of stress, characterized by high levels of HSP gene expression as well as HSF1-mediated non-HSP gene regulation. HSF1 and its gene targets are essential for tumorigenesis across several experimental tumor models, and facilitate metastatic and resistant properties within cancer cells. Recent studies have suggested the significant potential of HSF1 as a therapeutic target and have motivated research efforts to understand the mechanisms of HSF1 regulation and develop methods for pharmacological intervention. We review what is currently known regarding the contribution of HSF1 activity to cancer pathology, its regulation and expression across human cancers, and strategies to target HSF1 for cancer therapy.

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HSF5 Deficiency Causes Male Infertility Involving Spermatogenic Arrest at Meiotic Prophase I in Humans and Mice

Liu,

Wang,

et al. 2024

Advanced Science

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Meiosis is a specialized cell division process that generates gametes for sexual reproduction. However, the factors and underlying mechanisms involving meiotic progression remain largely unknown, especially in humans. Here, it is first showed that HSF5 is associated with human spermatogenesis. Patients with a pathogenic variant of HSF5 are completely infertile. Testicular histologic findings in the patients reveal rare postmeiotic germ cells resulting from meiotic prophase I arrest. Hsf5 knockout (KO) mice confirms that the loss of HSF5 causes defects in meiotic recombination, crossover formation, sex chromosome synapsis, and sex chromosome inactivation (MSCI), which may contribute to spermatocyte arrest at the late pachytene stage. Importantly, spermatogenic arrest can be rescued by compensatory HSF5 adeno‐associated virus injection into KO mouse testes. Mechanistically, integrated analysis of RNA sequencing and chromatin immunoprecipitation sequencing data revealed that HSF5 predominantly binds to promoters of key genes involved in crossover formation (e.g., HFM1, MSH5 and MLH3), synapsis (e.g., SYCP1, SYCP2 and SYCE3), recombination (TEX15), and MSCI (MDC1) and further regulates their transcription during meiotic progression. Taken together, the study demonstrates that HSF5 modulates the transcriptome to ensure meiotic progression in humans and mice. These findings will aid in genetic diagnosis of and potential treatments for male infertility.

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Targeted Deletion of Hsf1, 2, and 4 Genes in Mice

Cited by 14 publications

References 40 publications

Molecular Mechanisms of Heat Shock Factors in Cancer

Molecular Mechanisms of Heat Shock Factors in Cancer

HSF1: Primary Factor in Molecular Chaperone Expression and a Major Contributor to Cancer Morbidity

HSF5 Deficiency Causes Male Infertility Involving Spermatogenic Arrest at Meiotic Prophase I in Humans and Mice

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