Article
Medicine, Research & Experimental
Yujing Du, Zhao Chen, Ping Yan, Chunli Zhang, Xiaojiang Duan, Xueqi Chen, Meng Liu, Lei Kang, Xing Yang, Yan Fan, Jianhua Zhang, Rongfu Wang
Summary: The study identified heat shock protein 70 (HSP70) as the binding target for RRL, revealing a potential interaction between RRL and the nucleotide-binding domain (NBD) of HSP70. Clathrin-dependent endocytosis and macropinocytosis were suggested as vital internalization mechanisms of RRL. In vivo, Tc-99m-MAG3-RRL demonstrated satisfactory tumor accumulation and targeting, providing a promising probe for visualizing overexpressed HSP70 tumor sections.
MOLECULAR PHARMACEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Zifei Han, Shelli R. McAlpine, Robert Chapman
Summary: This study demonstrates the successful delivery of inhibitors to block the interaction between Hsp70 and HOP using polymer nanogels. The results show the effectiveness of these inhibitors in inhibiting Hsp70 and inducing cancer cell death.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Larissa Smulders, Rachel Altman, Carolina Briseno, Alireza Saatchi, Leslie Wallace, Maha AlSebaye, Robert Stahelin, Nikolas Nikolaidis
Summary: HSPA1A is a molecular chaperone that regulates the survival of stressed and cancer cells. It localizes to the plasma membrane of stressed and tumor cells and interacts with specific lipids, playing a role in immunomodulatory functions and rendering tumors resistant to treatment. This study reveals that the surface presentation of HSPA1A is a multifaceted lipid-driven phenomenon controlled by binding to endosomal and plasma membrane lipids.
Article
Biochemistry & Molecular Biology
Linan Xu, Hong Zhang, Daragh D. Cuskelly, Sean Doyle, Sarah Perrett, Gary W. Jones
Summary: Hsp70 is a conserved chaperone that plays a critical role in maintaining protein homeostasis. Mutations in the SBD disrupt its hydrophobic core, leading to impairment of heat-shock response and prion propagation. The disruption of key residues in the SBD region results in instability and cleavage of Hsp70, impacting its ATPase function and overall stability. This ultimately compromises the stress response and prion propagation abilities of yeast cells.
MOLECULAR MICROBIOLOGY
(2021)
Article
Plant Sciences
Koji Mikami, Ho Viet Khoa
Summary: Heat shock protein 70 (HSP70) is a conserved protein involved in maintaining protein folding and refolding in both prokaryotic and eukaryotic organisms. In the red alga Neopyropia yezoensis, we identified genes encoding HSP70 proteins in different cellular compartments. We found that membrane fluidization plays a role in the heat-induced expression of HSP70 genes in this alga. Our results suggest a unique regulatory system for heat-induced expression of HSP70 genes in N. yezoensis.
Article
Cell Biology
Sarah J. Backe, Rebecca A. Sager, Bethany R. Regan, Julian Sit, Lauren A. Major, Gennady Bratslavsky, Mark R. Woodford, Dimitra Bourboulia, Mehdi Mollapour
Summary: The chaperone machinery of heat shock protein-90 (Hsp90) is crucial for the stability and activity of its client proteins. Recent findings suggest that the co-chaperones FNIP1/2 and Tsc1 have an impact on Hsp90's client activity. They increase the affinity of steroid hormone receptors to their ligands, providing a model for the activation of these receptors.
Article
Chemistry, Physical
Julia Belyaeva, Alexander Zlobin, Valentina Maslova, Andrey Golovin
Summary: Classical molecular dynamics simulation is a powerful tool in computational chemistry, but accurate force fields are crucial for studying complex enzymatic systems. In this study, six force fields were tested on a serine triad protease trypsin complex, with diverging results. The best performing force fields were recommended for use in similar systems, and it is suggested to carefully consider force field choice in computational enzymology studies.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Mingzu Guo, Wenxi Xu, Yoshinari Yamamoto, Takuya Suzuki
Summary: The study found that curcumin can increase the expression of HSP70 in intestinal Caco-2 cells through transcriptional activation, possibly enhancing cell integrity. The effects of curcumin are regulated by various signaling pathways. This discovery is expected to contribute to a deeper understanding of the regulation of intestinal HSP70 by dietary components.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Multidisciplinary Sciences
Shanshan Li, Kan-Yen Hsieh, Chiao- Kuo, Shih-Chieh Su, Kai-Fa Huang, Kaiming Zhang, Chung- Chang
Summary: Lon protease is able to degrade protein substrates in a processive fashion at each of its six proteolytic active sites, forming a deep groove that encloses the substrate polypeptide chain and allows for continuous cleavage in the C-to-N direction. An acidic residue at the binding groove exit is identified as essential for the proteolytic activity, likely promoting processive proteolysis through carboxyl-carboxylate interactions with cleaved intermediates. These findings reveal a previously unrecognized mechanism for processive substrate degradation by the Lon protease.
Article
Biochemistry & Molecular Biology
Jie Yang, Weibin Gong, Si Wu, Hong Zhang, Sarah Perrett
Summary: Hsp70 proteins are ancient chaperones with important roles in cellular processes, making them potential drug targets for diseases like cancer. The inhibitor PES has been shown to interact with specific residues in Hsp70, affecting its structure and function similarly to glutathionylation. This study provides insights into developing covalent inhibitors for Hsp70.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Jana Skerlova, Jens Berndtsson, Hendrik Nolte, Martin Ott, Pal Stenmark
Summary: The pyruvate dehydrogenase complex (PDHc) is a multienzyme complex that converts pyruvate into acetyl-coenzyme A, linking glycolysis to the citric acid cycle. The core of PDHc is formed by dihydrolipoyl transacetylase, which provides binding sites for other enzymes and shuffles reaction intermediates between the active sites through covalently bound lipoyl domains. The cryo-EM structure of the E. coli dihydrolipoyl transacetylase core in a resting state reveals molecular details of the assembly and interactions at the active site.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Wei Wang, Qinglian Liu, Qun Liu, Wayne A. Hendrickson
Summary: Researchers characterized biochemical properties of selected domain-interface mutants in bacterial Hsp70 DnaK and developed a theoretical model to explain allosteric equilibria among Hsp70 conformational states. They proposed a restraining state and a stimulating state to describe the different characteristics of Hsp70 in ATP hydrolysis and peptide binding.
Article
Cell Biology
Luke A. A. Perera, David Ron
Summary: The ER-localized Hsp70 chaperone, BiP, undergoes a rapid and reversible modification called AMPylation, which complements the unfolded protein response in regulating protein folding demand in the ER. This modification is mediated by the enzyme FICD, which also has the ability to deAMPylate BiP. The structural basis of BiP recognition by FICD and the potential physiological significance of BiP AMPylation are also discussed.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2023)
Article
Agronomy
Chuanbei Tian, Yaying Li, Yixia Wu, Wenqiang Chu, Huai Liu
Summary: In fluctuating climatic environments, heat acclimation in predatory mites is a superior adaptation strategy for effective agricultural pest management. The sustained accumulation of HSP70 proteins results in predatory mites with thermotolerance advantage, promoting their biological control function to pests. The divergent constitutive regulation of HSP70 to a thermal environment allows predators to adapt flexibly to extreme stress.
PEST MANAGEMENT SCIENCE
(2021)
Article
Plant Sciences
S. Mukesh Sankar, C. Tara Satyavathi, Sharmistha Barthakur, Sumer Pal Singh, C. Bharadwaj Bharadwaj, S. L. Soumya
Summary: This study utilized transcript expression profiling to functionally clarify the role of small heat shock protein genes in pearl millet under high-temperature stress. Through analyzing the transcript expression pattern and physio-biochemical traits, genotypes such as WGI 126, TT-1, TT-6, and MS 841B were identified to respond positively towards high-temperature stress and exhibit better growth. The findings suggest the efficacy of transcript expression profiling as a molecular-based screening technique for identifying thermotolerant genes and genotypes at specific crop growth stages.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Stephen Tutton, Greggory A. Azzam, Nicholas Stong, Olga Vladimirova, Andreas Wiedmer, Jessica A. Monteith, Kate Beishline, Zhuo Wang, Zhong Deng, Harold Riethman, Steven B. McMahon, Maureen Murphy, Paul M. Lieberman
Article
Chemistry, Medicinal
Jaruwan Chatwichien, Subhasree Basu, Anna Budina-Kolomets, Maureen E. Murphy, Jeffrey D. Winkler
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2016)
Article
Oncology
Anna Budina-Kolomets, Marie R. Webster, Julia I-Ju Leu, Matthew Jennis, Clemens Krepler, Anastasia Guerrini, Andrew V. Kossenkov, Wei Xu, Giorgos Karakousis, Lynn Schuchter, Ravi K. Amaravadi, Hong Wu, Xiangfan Yin, Qin Liu, Yiling Lu, Gordon B. Mills, Xiaowei Xu, Donna L. George, Ashani T. Weeraratna, Maureen E. Murphy
Editorial Material
Cell Biology
Subhasree Basu, Maureen E. Murphy
Article
Oncology
Vito W. Rebecca, Michael C. Nicastri, Noel McLaughlin, Colin Fennelly, Quentin McAfee, Amruta Ronghe, Michel Nofal, Chun-Yan Lim, Eric Witze, Cynthia I. Chude, Gao Zhang, Gretchen M. Alicea, Shengfu Piao, Sengottuvelan Murugan, Rani Ojha, Samuel M. Levi, Zhi Wei, Julie S. Barber-Rotenberg, Maureen E. Murphy, Gordon B. Mills, Yiling Lu, Joshua Rabinowitz, Ronen Marmorstein, Qin Liu, Shujing Liu, Xiaowei Xu, Meenhard Herlyn, Roberto Zoncu, Donita C. Brady, David W. Speicher, Jeffrey D. Winkler, Ravi K. Amaravadi
Article
Oncology
Julia I-Ju Leu, Thibaut Barnoud, Gao Zhang, Tian Tian, Zhi Wei, Meenhard Herlyn, Maureen E. Murphy, Donna L. George
Article
Oncology
Anna Budina-Kolomets, Thibaut Barnoud, Maureen E. Murphy
CANCER BIOLOGY & THERAPY
(2018)
Article
Biology
Sunetra Roy, Karl-Heinz Tomaszowski, Jessica W. Luzwick, Soyoung Park, Jun Li, Maureen Murphy, Katharina Schlacher
Article
Multidisciplinary Sciences
Prashanth Gokare, Niklas K. Finnberg, Phillip H. Abbosh, Jenny Dai, Maureen E. Murphy, Wafik S. El-Deiry
SCIENTIFIC REPORTS
(2017)
Article
Multidisciplinary Sciences
Julia I-Ju Leu, Maureen E. Murphy, Donna L. George
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Review
Biochemistry & Molecular Biology
Thibaut Barnoud, Alexandra Indeglia, Maureen E. Murphy
Summary: The TP53 gene remains the most frequently mutated gene in cancer, driving intense research efforts to understand its role in tumor suppression. The journey towards understanding p53 function has been complex and challenging, leading to paradigm shifts and emerging challenges for future research. This review provides a valuable historical reference for those interested in p53 and highlights the importance of flexibility in the face of established paradigms.
Article
Biochemistry & Molecular Biology
Keerthana Gnanapradeepan, Alexandra Indeglia, David C. Stieg, Nicole Clarke, Chunlei Shao, James F. Dougherty, Nivitha Murali, Maureen E. Murphy
Summary: The tumor suppressor protein p53 plays a crucial role in suppressing cancer by regulating processes such as cell death and growth inhibition. This study identifies PLTP as a p53 target gene that is highly sensitive to p53 transcriptional function and is involved in growth suppression and ferroptosis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Editorial Material
Oncology
David Stieg, Kaitlyn Casey, Maureen E. Murphy
Summary: In this issue of Cancer Discovery, the Prives and Lozano groups present companion articles discussing the functional analysis of a frequently occurring mutant of p53, A347D, in Li-Fraumeni disease and sporadic cancer. The authors demonstrate that this mutant has a complete loss of canonical p53 transcriptional function, but retains some tumor suppressor properties, manifested as neomorphic activities in transcription and control of mitochondrial metabolism.
Article
Oncology
Julia I-Ju Leu, Maureen E. Murphy, Donna L. George
Summary: The tumor protein P53 has intricate and sometimes conflicting roles in regulating metabolism and ferroptosis sensitivity. Its actions influence the redox state, affecting redox-sensitive proteins and modifying metabolic processes and response to ferroptosis.
MOLECULAR & CELLULAR ONCOLOGY
(2021)
Article
Oncology
Che-Pei Kung, Qin Liu, Maureen E. Murphy
CANCER BIOLOGY & THERAPY
(2017)