Review
Gastroenterology & Hepatology
May San Martinho, Derek J. Nancarrow, Theodore S. Lawrence, David G. Beer, Dipankar Ray
Summary: The incidence of esophageal adenocarcinoma and other gastrointestinal cancers is rising, emphasizing the need to identify oncogenic drivers to develop effective therapies. Targeting molecular chaperones that mediate mutant p53 stability may prove to be an effective strategy in improving cancer outcomes. Targeting the interaction of mutant p53 with E3 ubiquitin ligase isoforms like GRAIL could help mitigate esophageal adenocarcinoma development.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Guiyou Tian, Cheng Hu, Yun Yun, Wensheng Yang, Wolfgang Dubiel, Yabin Cheng, Dieter A. Wolf
Summary: The study reveals the selective upregulation of HSP70-family chaperone HSPA1 and its co-factors, HSPH1 and DNAJB1, in breast cancer cells acquiring thermotolerance. HSPA1 plays dual roles in heat stress response, promoting protein degradation and synthesis during acute stress, and maintaining newly synthesized proteins in a soluble state during thermotolerance. Deletion of HSPH1 impedes thermotolerance and esophageal tumor growth in mice, suggesting a potential therapeutic target for cancer.
Article
Biochemistry & Molecular Biology
Abramo J. Manfredonia, Daniel A. Kraut
Summary: The ubiquitin-proteasome system is responsible for protein degradation in eukaryotic cells. The study showed that degradation of ubiquitin-independent degrons (UbIDs) is slower and relies on loosely folded substrates. Furthermore, UbID degradation is ATP-independent.
Article
Chemistry, Medicinal
Sun-Young Han
Summary: Target protein degraders are a new paradigm in small molecule drug discovery, important for treating acute myeloid leukemia. Strategies to overcome resistance to current FLT3 kinase inhibitors are needed. Small molecules that downregulate FLT3 protein level have shown antileukemic effects.
Article
Biochemistry & Molecular Biology
Florian Job, Carolin Mai, Pablo Villavicencio-Lorini, Juliane Herfurth, Herbert Neuhaus, Katrin Hoffmann, Thorsten Pfirrmann, Thomas Hollemann
Summary: Ubiquitination and deubiquitylation are crucial processes in cells, and OTUD3 is a conserved deubiquitinase that plays a role in cellular homeostasis, particularly in neuronal tissues. OTUD3 is found in the cytoplasm and binds to microtubules. It preferentially cleaves poly-ubiquitin linkages at K6 and K63, which are not primarily involved in protein degradation. Suppression of otud3 function in early neural development results in impaired formation of cranial and cranial neural crest-derived structures, as well as movement defects. Thus, OTUD3 is a neuronally enriched deubiquitinase that is important for proper neural system development.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2023)
Article
Multidisciplinary Sciences
Donghoon Lee, Alfred L. Goldberg
Summary: Heat shock induces protein unfolding, leading to increased activity of proteasomes and degradation of ubiquitinated proteins. This response helps cells clear damaged proteins and maintain cellular homeostasis under proteotoxic stress conditions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Carolyn Allain Breckel, Mark Hochstrasser
Summary: The proper folding of proteins is vital for their diverse functions, and misfolded proteins can potentially harm cells by forming aggregates. Protein quality control pathways are responsible for repairing or degrading abnormal proteins, with the ubiquitin-proteasome system being commonly employed.
Review
Plant Sciences
Pei An, Li-Jun Zhang, Wei Peng, Yu-Ying Chen, Qiu-Ping Liu, Xin Luan, Hong Zhang
Summary: The study reviewed the pharmacological effects of more than 80 natural products and extracts related to proteasome regulation, classified them by their chemical properties, and summarized the laws of action of natural products as proteasome regulators in the treatment of diseases, which is important for the discovery of new proteasome regulators.
Review
Cell Biology
Michael Basler, Marcus Groettrup
Summary: The immunoproteasome is a special type of proteasome induced under inflammatory conditions, contributing to protein homeostasis in cells and involved in immune response, T cell expansion, and inflammatory diseases. Targeting the immunoproteasome has shown therapeutic effectiveness in cancer, autoimmune diseases, and transplantation in preclinical animal models.
Article
Multidisciplinary Sciences
Afu Fu, Victoria Cohen-Kaplan, Noa Avni, Ido Livneh, Aaron Ciechanover
Summary: The degradation of proteins through the ubiquitin-proteasome system is a complex multistep process that relies on the coordinated activity of various enzymes. Nuclear condensates containing essential components like p62 play a crucial role in protein quality control and degradation, especially under stress conditions. These assemblies, generated through liquid-liquid phase separation, efficiently facilitate proteolysis of nuclear proteins and unassembled proteasome subunits, indicating their involvement in cellular protein quality control.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Hangjun Sun, Xinxin Jing, Chaonan Wang, Pengyue Wang, Ziting Huang, Bingjian Sun, Pengbai Li, Honglian Li, Chao Zhang
Summary: Plant viruses cause significant damage to global crop production and plants activate defense signaling pathways to hinder virus propagation. Protein homeostasis regulation plays a vital role in the ongoing battle between plants and viruses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Aditi Sharma, Om Prakash Shah, Lalit Sharma, Monica Gulati, Tapan Behl, Asaad Khalid, Syam Mohan, Asim Najmi, Khalid Zoghebi
Summary: Misfolded and aggregated proteins are the main cause of neurodegenerative diseases, and molecular chaperones play a crucial role in controlling this process. Aging affects the function of molecular chaperones, leading to increased aggregation of misfolded proteins and the development of neurodegenerative diseases. Molecular chaperones are also linked to diseases such as Parkinson's, Huntington's, and Alzheimer's. Therefore, they have the potential to be therapeutic targets for brain disorders.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Vasudha Tandon, Rita Moreno, Kira Allmeroth, Jean Quinn, Sandra E. Wiley, Lynden G. Nicely, Martin S. Denzel, Joanne Edwards, Laureano de la Vega, Sourav Banerjee
Summary: Preserving proteostasis is a crucial survival mechanism for cancer, and targeting the kinase DYRK2 and its substrate HSF1 can induce apoptosis faster than individual targeting. This study suggests that cotargeting DYRK2 and HSF1 could be a promising strategy in suppressing cancer.
BIOSCIENCE REPORTS
(2023)
Review
Cell Biology
Yosup Kim, Eun-Kyung Kim, Yoona Chey, Min-Jeong Song, Ho Hee Jang
Summary: The proteasome is a multi-catalytic protease complex that regulates protein quality control. It selectively degrades cellular proteins through ubiquitination and plays a critical role in maintaining protein homeostasis. This article summarizes the proteasome's structure, regulatory mechanisms, proteins that control its activity, and its involvement in various diseases, chemoresistant cells, and cancer stem cells. Potential therapeutic modalities that target the ubiquitin-proteasome system are also discussed.
Review
Biochemistry & Molecular Biology
Yanhui Zhou, Hakim Manghwar, Weiming Hu, Fen Liu
Summary: Autophagy is a key pathway for nutrient recycling in eukaryotes, influenced by various factors such as hormones, second messengers, post-transcriptional regulation, and protein post-translational modification. It is activated under stress conditions to help cells survive, and the degradation mechanism of autophagy-related proteins in different organisms has attracted attention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)