HSF4

更新于：2025-05-07

基本信息

别名

CTM、Heat shock factor protein 4、heat shock transcription factor 4

+ [4]

简介

Heat-shock transcription factor that specifically binds heat shock promoter elements (HSE) (PubMed:22587838, PubMed:23507146). Required for denucleation and organelle rupture and degradation that occur during eye lens terminal differentiation, when fiber cells that compose the lens degrade all membrane-bound organelles in order to provide lens with transparency to allow the passage of light (By similarity). In this process, may regulate denucleation of lens fiber cells in part by activating DNASE2B transcription (By similarity). May be involved in DNA repair through the transcriptional regulation of RAD51 (PubMed:22587838). May up-regulate p53/TP53 protein in eye lens fiber cells, possibly through protein stabilization (PubMed:28981088). In the eye lens, controls the expression of alpha-crystallin B chain/CRYAB and consequently may be involved in the regulation of lysosomal acidification (By similarity). Transcriptional repressor. Transcriptional activator.

关联

100 项与 HSF4 相关的临床结果

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100 项与 HSF4 相关的转化医学

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0 项与 HSF4 相关的专利（医药）

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325

项与 HSF4 相关的文献（医药）

2025-05-01·Gene

Crosstalk between signaling pathways (Rho/ROCK, TGF-β and Wnt/β-Catenin Pathways/ PI3K-AKT-mTOR) in Cataract: A Mechanistic Exploration and therapeutic strategy

Review

作者: Verma, Lokesh ; Khan, Meraj

Cataract are a leading cause of visual impairment that is characterized by clouding or lens opacification of the healthy clear lens of the eye or its capsule. It can be classified based on their etiology and clinical presentation such as congenital, age-related, and secondary cataracts. Clinically, it may be further classified as a cortical or nuclear cataract. Cortical cataracts are responsible for opacification of the lens cortex, while nuclear cataracts cause age-related degeneration of the lens nucleus. This review aims to explore the molecular mechanism associated with various signaling pathways underlying cataract formation. Additionally, explore the potential therapeutic strategies for the management of cataracts. A comprehensive literature search was performed utilizing different keywords such as cataract, pathogenesis, signaling pathways, therapeutic approaches, RNA therapeutics, and surgery. Electronic databases such as PubMed, Google Scholar, Springer Link, and Web of Science were used for the literature search. The cataract formation is responsible for protein aggregation, primarily of γ-crystallin, and causes disruptions in signaling pathways. Key pathways include Rho/ROCK, TGF-β, Wnt/β-catenin, NF-κB, and PI3K-AKT-mTOR. Signaling pathways governing lens epithelial cell differentiation and epithelial-to-mesenchymal transition (EMT) are essential for maintaining lens transparency. Disruptions in these pathways, often caused by genetic mutations in genes like MIP, TDRD7, PAX6, FOXE3, HSF4, MAF, and PITX3 lead to cataract formation. While surgical intervention remains the primary treatment, pharmacological therapies and emerging RNA-based strategies offer promising strategies for the prevention and management of cataracts. A deeper understanding of the underlying molecular mechanisms is essential to develop innovative therapeutic strategies and improve the quality of life for individuals affected by cataracts.

2025-05-01·Experimental Eye Research

Genetic mutation in HSF4 is associated with retinal degeneration in mice

Article

作者: Jiang, MingJun ; Hu, Yanzhong ; Lang, Youfei ; Peng, Xuyan ; Liu, Baixue ; Li, Yujie ; Jia, Xiaolin ; Xue, Mengjiao

Genetic mutations in Hsf4 cause developmental defect of lens at postnatal age. However, the regulatory effect of Hsf4 mutations on retinal homeostasis have not been elucidated. Here we found that HSF4 expresses in retinal and its expression level decrease with age increase. Using Hsf4^del mice, which express a Hsf4 mutant with deletion of 42 amino acids in-frame- in the N-terminal hydrophobic region and develop cataracts at P27, we found that Hsf4^del mutation downregulated the expression of visual cycle regulatory proteins, RPE65, RDH5 and RLBP1 and heat shock proteins HSP25 and HSP90, but upregulated retinal gliosis and senescence-associated proteins such as cycle-inhibitors P21 and P16 in P10 retina without change retinal structure. With age increase Hsf4^del mice undergo retinal degeneration, characterized by thinner ONL, disorganized INL, disconnected RPE, neovascularization, and lipofuscin deposits. ERG results showed that the amplitudes of a- and b-waves at dark adaption were reduced in Hsf4^del mice at P15, worsening with age. Intravitreal injection of AAV-Flag-Hsf4b in one-month-old Hsf4^del mice partially restored the expression of visual cycle proteins and ERG responses and reduced the gliosis. Studies in vitro indicated that Hsf4 is able to bind to promoters of RPE65 and RDH5. Altogether, these data suggest that Hsf4 participates in regulating the expression of retinal visual cycle-regulatory proteins in addition to heat shock proteins during early retinal development. Genetic mutations in Hsf4 is associated with not only congenital cataracts but also retinal degeneration.

2025-04-01·Journal of Cellular Biochemistry

Deficiency of HSF4 Increases the Secretion of Small Extracellular Vesicles via Upregulation of Chaperone‐Mediated Autophagy

Article

作者: Mao, Yi ; Xue, Mengjiao ; Shao, Jingzhi ; Jiang, Mingjun ; Liu, Xuhui ; Zhang, Fengyan ; Liu, Jingjing ; Si, Wei ; Hu, Yanzhong ; Zhang, Yuhang ; Du, Shanshan ; Peng, Xuyan ; Xie, Xiaohang

ABSTRACTSmall extracellular vesicles (SEVs) are membrane‐bound vesicles secreted by cells that facilitate intercellular communication. This study reveals how heat shock transcription factor 4 (HSF4) deficiency regulates SEV secretion in lens epithelial cells through chaperone‐mediated autophagy (CMA). Compared to mLEC/HA‐Hsf4b cells, SEVs secreted by HSF4‐deficient mLEC/Hsf4−/− cells showed significantly increased levels of CMA‐related proteins (HSP70, HSC70, LAMP2A, and HSP90) and EGFR, while LC3 II levels were reduced. Additionally, EGFR‐enriched SEVs activated downstream ERK/AKT signaling pathways, promoting the proliferation and migration of lens epithelial cells and inducing epithelial–mesenchymal transition (EMT). Further inhibition experiments showed that blocking HSP70 and HSP90 with apoptozole and retaspimycin, or silencing LAMP2A with siRNA, reduced SEV secretion in HSF4‐deficient cells. Collectively, enhanced CMA activity and increased SEV secretion induced by HSF4 deficiency may represent a potential mechanism underlying congenital cataract development.

项与 HSF4 相关的新闻（医药）

2023-07-23

·生物探索

前列腺癌雄激素受体靶向治疗耐药的潜在机制

肿瘤的突变负担和异质性已被认为是对许多靶向治疗产生耐药性的原因。胞嘧啶脱氨酶APOBEC蛋白与超过70%的人类癌症的突变特征有关。然而，癌细胞如何劫持APOBEC介导的突变机制以促进肿瘤异质性，从而促进治疗耐药性的机制尚不清楚。2023年7月20日，德克萨斯大学西南医学中心牟平团队在Cancer Cell 在线发表题为“Loss of SYNCRIP unleashes APOBEC-driven mutagenesis, tumor heterogeneity, and AR-targeted therapy resistance in prostate cancer”的研究论文，该研究发现SYNCRIP是一种内源性分子制动器，可以抑制前列腺癌(PCa)中APOBEC驱动的突变。在SYNCRIP缺失的PCa细胞中，过度激活的APOBEC3B是一个关键的突变子，代表了PCa中一些常见突变基因(包括FOXA1、EP300)驱动突变的分子来源。功能筛选确定了APOBEC3B突变的PCa中雄激素受体(AR)靶向治疗耐药的8个关键驱动因素：BRD7、CBX8、EP300、FOXA1、HDAC5、HSF4、STAT3和AR。这些结果揭示了APOBEC驱动的突变释放的细胞内在机制，该机制在赋予PCa AR靶向治疗耐药中起重要作用。针对驱动癌基因的治疗方法的发展已经彻底改变了许多癌症的临床管理；然而，它们的反应的幅度和持续时间仍然是可变的，并且不可避免地发生抵抗。大量证据表明，突变负担的增加和遗传异质性既是抗性的燃料，也是抗性的来源。因此，阐明这种增加的诱变和遗传异质性的分子起源和机制对于培养下一代抗癌疗法和克服耐药性至关重要。遗传异质性可能源于许多癌症的基因组不稳定性。新出现的数据表明，肿瘤细胞可以劫持稳态调节机制，从而加强突变，作为促进基因组不稳定的可能途径。这种机制的一个重要例子是脱氨酶APOBEC蛋白。在超过70%的人类癌症中观察到APOBEC驱动的突变模式增加。然而，癌细胞如何劫持APOBEC介导的突变机制以促进肿瘤异质性，从而促进治疗耐药性的机制在很大程度上仍然未知。机理模式图（图源自Cancer Cell ）该研究发现前列腺癌(PCa)中突触结合细胞质RNA相互作用蛋白(SYNCRIP)的频繁丢失是一个分子驱动事件，释放APOBEC驱动的突变。在SYNCRIP缺失的肿瘤中，过度激活的APOBEC3B是PCa(包括FOXA1、EP300和AR)中频繁驱动突变的关键突变子和分子来源。研究结果确定了8个由APOBEC3B失调引起的PCa雄激素受体(AR)靶向治疗耐药的关键驱动因素。与传统认识相反，单细胞转录组学分析显示，APOBEC3B诱导的FOXA1驱动突变胜过其他驱动突变，最终主导耐药肿瘤。总的来说，这些发现揭示了控制肿瘤突变负担和异质性的细胞内在机制，并将SYNCRIP和过度激活的APOBEC3B驱动的突变与经常观察到的赋予AR靶向治疗耐药性的驱动突变在机制上联系起来。文章来源“iNature”责编|文竞择校对|文竞择End 往期精选围观历史性突破！不需卵子和精子就可以合成人类胚胎热文富豪用儿子血浆“回春”科学吗？Science：血液牛磺酸缺乏驱动衰老热文世界首例！35岁的她，通过机器人操刀移植的子宫，成功诞下宝宝热文‍为了避免心脏骤停，53岁的他成为“第一个”植入开创性除颤器的心脏病患者热文首次披露！175家生物制药公司的薪资数据：薪资中位数达20万美元点击“阅读原文”，了解更多~

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