Article
Biochemistry & Molecular Biology
Robert F. Shearer, Dimitris Typas, Fabian Coscia, Sofie Schovsbo, Thomas Kruse, Andreas Mund, Niels Mailand
Summary: Ubiquitin conjugation to substrate proteins regulates cellular processes and the K27 linkage type is essential for human cell proliferation. K27-linked ubiquitylation predominantly occurs in the nucleus and its disruption impairs nuclear ubiquitylation dynamics and cell cycle progression. K27-linked ubiquitylation supports cell fitness by facilitating p97-dependent processing of ubiquitylated nuclear proteins.
Review
Biochemistry & Molecular Biology
Justin B. Gregor, Dantong Xu, Michael E. French
Summary: Protein ubiquitylation is a crucial modification that regulates various aspects of eukaryotic cell biology. Ubiquitin chains can be branched and this branching directly affects the stability or activity of the target proteins. This review discusses the mechanisms controlling the assembly and disassembly of branched chains by ubiquitylation enzymes and deubiquitylases. It also summarizes the activities of chain branching ubiquitin ligases and deubiquitylases responsible for cleaving branched chains, as well as recent findings on the formation of branched chains and selective debranching by UCH37.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Anmol Sharma, Heena Khan, Thakur Gurjeet Singh, Amarjot Kaur Grewal, Agnieszka Najda, Malgorzata Kawecka-Radomska, Mohamed Kamel, Ahmed E. Altyar, Mohamed M. Abdel-Daim
Summary: The ubiquitin-proteasome pathway is crucial in regulating various biological functions and plays a significant role in tumor development. Inhibiting specific enzymes within this pathway can be an effective treatment for cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Xiao Yuan, Xiaoman Zhang, Huan Wang, Xiang Mao, Yingjie Sun, Lei Tan, Cuiping Song, Xusheng Qiu, Chan Ding, Ying Liao
Summary: This study reveals the important role of the ubiquitin-proteasome system (UPS) in coronavirus entry. Inhibition of UPS severely impairs the infectivity of infectious bronchitis virus (IBV) and porcine epidemic diarrhea virus (PEDV). UPS inhibition prevents the membrane fusion of IBV and PEDV with late endosomes or lysosomes, blocking virus uncoating, initial translation, and replication events.
Review
Oncology
Grazia R. Tundo, Diego Sbardella, Francesco Oddone, Anna A. Kudriaeva, Pedro M. Lacal, Alexey A. Belogurov, Grazia Graziani, Stefano Marini
Summary: The immunoproteasome plays a crucial role in antigen presentation and its modulation presents promising research opportunities. Immunotherapy has shown significant advancements, however, a broader understanding of cancer cell antigen processing dynamics is still required for further improvements.
Review
Cell Biology
Satyendra Chandra Tripathi, Disha Vedpathak, Edwin Justin Ostrin
Summary: Cell-mediated immunity is driven by antigenic peptide presentation on major histocompatibility complex (MHC) molecules. Immunoproteasomes, with inducible activity by inflammatory stimuli, play central roles in cancer, autoimmunity, and inflammation by altering the catalytic activity of the proteasome.Understanding the roles of immunoproteasome in different cancers offers insights into developing targeted therapies.
Review
Cell Biology
Yusuke Nishimura, Ibrahim Musa, Lars Holm, Yu-Chiang Lai
Summary: Skeletal muscle protein turnover is crucial for maintaining muscle mass and quality control, with the ubiquitin proteasome system playing a key role in protein degradation. Exercise is a recognized nonpharmacological approach to promote muscle protein turnover rates, but there are still challenges in understanding the molecular mechanisms of muscle protein degradation.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Review
Oncology
Priyanka S. Rana, James J. Ignatz-Hoover, James J. Driscoll
Summary: Proteasomes are complex protein-degrading machines that regulate the elimination of intracellular proteins. Immunoproteasomes are a specialized variant that degrade proteins in cells exposed to oxidative stress and inflammation. They can be targeted for therapeutic purposes in the treatment of cancer and infectious diseases.
Review
Oncology
Chee Wai Fhu, Azhar Ali
Summary: The UPS system regulates the non-lysosomal degradation of oxidized, damaged, or misfolded proteins through the activation and transfer of polyubiquitin chains to target proteins, which are then degraded by the 26S proteasome complex. UPS plays a crucial role in regulating protein levels to maintain fundamental cellular processes such as growth, division, signal transduction, and stress response. Dysregulation of UPS, resulting in loss of ability to maintain protein quality through proteolysis, is closely related to the development of various malignancies.
Article
Biochemistry & Molecular Biology
Hao Li, Shuangshuang Shu, Miaomiao Zhou, Ying Chen, An Xiao, Yuanyuan Ma, Fengxin Zhu, Zheng Hu, Jing Nie
Summary: In this study, researchers found that Numb, an adaptor protein, increases the protein abundance of DEPTOR by inhibiting the ubiquitination mediated by SCF beta-TrCP2, leading to increased autophagy flux. Numb disrupts the interaction between beta-TrCP2 and SKP1 by directly binding with SKP1. In a mouse model of renal fibrosis, Numb expression was significantly increased and depletion of Numb reduced DEPTOR abundance and attenuated autophagy in fibrotic lesions. These findings indicate that Numb plays an important role in regulating autophagy.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Oncology
Srirupa Bhattacharyya, Janet L. Oblinger, Roberta L. Beauchamp, Zhenzhen Yin, Serkan Erdin, Priya Koundinya, Anna D. Ware, Marc Ferrer, Justin T. Jordan, Scott R. Plotkin, Lei Xu, Long-Sheng Chang, Vijaya Ramesh
Summary: This study identifies a class of compounds targeting the ubiquitin-proteasome pathway (UPP) that have potent efficacy in treating NF2-associated tumors. These compounds reduce cell viability and induce apoptosis by downregulating c-KIT and PDGFR alpha expression and upregulating genes associated with endoplasmic reticulum stress-mediated activation of the unfolded protein response (UPR). In vivo models further demonstrate the therapeutic potential of these drugs.
Review
Biochemistry & Molecular Biology
Olga Buneeva, Alexei Medvedev
Summary: Ubiquitination is a major post-translational modification of proteins, and atypical ubiquitination plays a crucial role in the development of Parkinson's disease, targeting proteins involved in the disease mechanism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Peifeng Yu, Zhihua Hua
Summary: The ubiquitin-26S proteasome system and autophagy are two major protein degradation machineries in eukaryotic organisms. They function to maintain proteome homeostasis by degrading short-lived and/or soluble misfolded proteins under normal conditions, and long-lived aggregated proteins and damaged organelles under stress conditions. Recent discoveries have revealed an integrative function of these systems, with ubiquitin playing a central role in their reciprocal degradation. This review summarizes current knowledge about the control of proteasome and autophagosome activity, and presents new research directions for understanding the molecular mechanisms underlying protein degradation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Betsegaw Lemma, Di Zhang, Ganga B. Vamisetti, Bryan G. Wentz, Hiroaki Suga, Ashraf Brik, Jacek Lubkowski, David Fushman
Summary: The mechanism of affinity and binding selectivity of cyclic peptides with polyubiquitin chains has been uncovered, along with the requirements for preferential selection of specific structures in longer polyubiquitin chains. These structural insights will guide the development of next-generation cyclic peptides with enhanced anti-cancer activity.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Liang Ren, Bei Xu, Jiadai Xu, Jing Li, Jifeng Jiang, Yuhong Ren, Peng Liu
Summary: A UBBRS risk score model was established by selecting UPPGs associated with overall survival of MM patients, which can predict the survival of MM patients and identify patients who would benefit more from PIs treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Kun He, Mengyi Xie, Weifeng Hong, Yonghe Li, Yaolin Yin, Xiaojin Gao, Yi He, Yu Chen, Chuan You, Jingdong Li
Summary: Centromere protein L (CENPL) is overexpressed in hepatocellular carcinoma (HCC) and is associated with poor patient prognosis. Upregulation of CENPL promotes tumor proliferation and glycolysis in HCC cells by activating the MEK1/2-ERK1/2 signaling pathway.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Article
Biochemistry & Molecular Biology
Yingzi Wang, Haozhong Huang, Huimin Weng, Chunsen Jia, Bin Liao, Yang Long, Fengxu Yu, Yongmei Nie
Summary: Talin protein plays a crucial role in transmitting mechanical forces by connecting the extracellular matrix to the cytoskeleton. It converts mechanical signals into biochemical signals and serves as diagnostic, therapeutic, and prognostic indicators in diseases.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Review
Biochemistry & Molecular Biology
Hema Saranya Ilamathi, Marc Germain
Summary: Mitochondria are the central metabolic hubs in cells, relying on proteins encoded by nuclear DNA and mitochondrial DNA (mtDNA) for their function. The maintenance and distribution of mtDNA are crucial for proper mitochondrial function and are associated with mitochondrial diseases. mtDNA is organized into nucleoids that dynamically move and interact with each other. The replication and distribution of mtDNA nucleoids are regulated by the complex interplay of mitochondrial dynamics, ER-mitochondria contact sites, and cytoskeletal networks.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Article
Biochemistry & Molecular Biology
K. K. Sruthi, Sirisha Natani, Ramesh Ummanni
Summary: The overexpression of TPD52 is associated with the emergence of neuroendocrine prostate cancer (NEPC). TPD52 activates the NF-kappa B - STAT3 axis to induce neuroendocrine differentiation (NED) of prostate cancer cells. Therapeutic targeting of TPD52 is important for the treatment of prostate cancer.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Article
Biochemistry & Molecular Biology
Cui Li, Feifan Xiang, Yuqi Gong, Yi Fu, Ge Chen, Zhi Wang, Zhong Li, Daiqing Wei
Summary: Our study demonstrates the significant role of tumor-derived microparticles (T-MPs) in osteosarcoma metastasis and immune response. T-MPs promote macrophage polarization and stimulate migration and chemoresistance of osteosarcoma cells, thereby affecting the progression of osteosarcoma.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)