Article
Biochemistry & Molecular Biology
Mahamat Babagana, Lorin R. Brown, Hannah Z. Slabodkin, Julia V. Kichina, Eugene S. Kandel
Summary: Hyperactivity of AKT in cancer cells leads to increased sensitivity to proteotoxic stress, manifested by heightened response to heat shock and greater dependence on XBP1 for growth. This stress-induced vulnerability can be exploited for therapeutic targeting.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Gisela Mazaira, Pablo C. Echeverria, Sol M. Ciucci, Martin Monte, Luciana Gallo, Alejandra G. Erlejman, Mario D. Galigniana
Summary: The dimerization of Hsp90 plays a crucial role in the chaperone complex associated with GR. Co-chaperones with TPR domains impact the biological properties and transport of GR, leading to different subcellular distributions and transcriptional activities. The relative abundance of TPR domain interacting co-chaperones may contribute to the pleiotropic actions of GR in different cell types.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Vinay Dahiya, Daniel Andreas Rutz, Patrick Moessmer, Moritz Muehlhofer, Jannis Lawatscheck, Matthias Rief, Johannes Buchner
Summary: This study reveals the crucial role of the co-chaperone Hop in the folding process of stringent clients, facilitating the transfer and folding of clients through its interaction with Hsp70 and Hsp90.
Review
Biochemistry & Molecular Biology
Stefan Tukaj, Krzysztof Sitko
Summary: Over a hundred different autoimmune diseases have been described to date, affecting various organs including the skin. The loss of immune tolerance in autoimmune diseases leads to chronic inflammation and tissue damage. Current treatments focus on immunosuppression but may cause serious adverse effects. Heat shock proteins Hsp90 and Hsp70 have been identified as potential therapeutic targets for autoimmune skin diseases.
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
Zeynep Eroglu, Y. Ann Chen, Inna Smalley, Jiannong Li, Joseph K. Markowitz, Andrew S. Brohl, Leticia Tetteh, Hayley Taylor, Vernon K. Sondak, Nikhil I. Khushalani, Keiran S. M. Smalley
Summary: In this study, the efficacy and safety of vemurafenib and cobimetinib in combination with different doses of the HSP90 inhibitor XL888 for the treatment of advanced melanoma were explored. The study found that this combination therapy showed activity in some patients, but also had significant toxicity.
Article
Biochemistry & Molecular Biology
Tanya Ju-Ngam, Nichanun McMillan, Mamoru Yoshimizu, Hisae Kasai, Ratree Wongpanya, Prapansak Srisapoome
Summary: This research conducted molecular characterization and biofunctional analyses of Hsp40 and Hsp90 genes in giant river prawns under various stress conditions. The highest similarity scores of these genes were found with crustaceans. Expression patterns of Mr-hsp40 and Mr-hsp90 were different under Aeromonas hydrophila challenge and heat-cold shock conditions, highlighting their significant roles in stress responses.
Article
Pharmacology & Pharmacy
Lihong Li, Man Yang, Chenyao Li, Yajun Liu
Summary: HSP90 is a crucial molecular chaperone involved in cancer processes and is considered a promising target for anticancer drug development. Miltefosine and Octenidine were identified as new HSP90 inhibitors with strong and broad-spectrum anticancer activity, disrupting the chaperone function of HSP90.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Review
Medicine, Research & Experimental
Yeh Chin, Khanisyah E. Gumilar, Xing-Guo Li, Brahmana A. Tjokroprawiro, Chien-Hsing Lu, Jianrong Lu, Ming Zhou, Robert W. Sobol, Ming Tan
Summary: HSF1 is a master regulator of heat shock responsive signaling and also regulates a non-heat shock responsive transcriptional network. It plays important roles in cellular transformation and cancer development. Research on HSF1 has been active due to its critical functions in handling stressful cellular states. New functions and molecular mechanisms have been continuously discovered, providing new targets for cancer treatment strategies. This article reviews the essential roles and mechanisms of HSF1 in cancer cells, focusing on recently discovered functions and their underlying mechanisms, as well as advances in HSF1 inhibitors for cancer drug development.
Article
Cell & Tissue Engineering
Ju-Fang Liu, Po-Chun Chen, Thai-Yen Ling, Chun-Han Hou
Summary: This study demonstrates that heat shock induces the expression of HSPs in hPDMCs through the activation of ROS, p38 MAPK, Akt signaling, and HSF1, which plays a protective role.
STEM CELL RESEARCH & THERAPY
(2022)
Review
Cell Biology
Xiude Ren, Tao Li, Wei Zhang, Xuejun Yang
Summary: Heat-shock protein 90 (HSP90) is an important molecule chaperone associated with tumorigenesis and malignancy. It plays a role in the malignant behaviors of cancer cells, but currently there are no effective single-agent treatments. Combining HSP90 inhibitors with other anticancer therapies may be a better strategy.
Article
Biochemistry & Molecular Biology
Wen-Cheng Lu, Ramsey Omari, Haimanti Ray, John Wang, Imade Williams, Curteisha Jacobs, Natasha Hockaden, Matthew L. Bochman, Richard L. Carpenter
Summary: The heat stress response activates the transcription factor HSF1, which upregulates heat shock proteins to maintain the integrity of the proteome. This study identifies multiple kinases involved in the phosphorylation of HSF1, with AKT1 being the most potent activator. The study also reveals previously unknown phosphorylation sites on HSF1 and their important roles in HSF1 trimerization, gene transactivation, and recruitment of proteins. Overall, this study highlights the targeted hyperphosphorylation of HSF1 and the functional significance of specific phosphorylation sites in regulating its transcriptional activity.
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
Cell Biology
Shuangshuang Yang, Tingting Zhao, Aijun Ma, Zhihui Huang, Jingkun Yang, Chenhao Yuan, Xiaoli Guo, Chunyue Zhu
Summary: The study found that heat stress activates ERK1/2 and HSF1, inducing HSP90 gene expression in turbot kidney cells. Inhibition of ERK activation reduces heat stress-induced HSP90 gene expression. This is the first report on the signaling pathway regulating the heat shock response in turbot cells, providing insights into molecular mechanisms of cellular stress response in marine fish.
CELL STRESS & CHAPERONES
(2021)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)