Article
Biochemistry & Molecular Biology
Chenliang Zhang, Qiulin Tang, Hongwei Xia, Huanji Xu, Feng Bi
Summary: Protein aggregation and degradation via autophagy (aggrephagy) are important cellular mechanisms to remove misfolded polypeptides when proteasome function is impaired. A protein complex consisting of heat shock protein 70 (Hsp70), cochaperone CHIP, and co-chaperone BAG3 has been shown to be involved in activating protein aggregation. However, the specific mechanisms of how this complex functions in protein degradation are not yet well understood. This study reveals that the M2 isoform of pyruvate kinase (PKM2) promotes the aggregation of ubiquitinated proteins under proteasome stress. Knockout or knockdown of PKM2 worsens the sensitivity of cells to proteasome inhibitors. Additionally, PKM2 facilitates the interaction between BAG3, CHIP, and HSP70 upon proteasome inhibition. These findings suggest that PKM2 plays a regulatory role in the formation of the CHIP-HSP70-BAG3 complex and promotes the aggregation of ubiquitinated misfolded proteins in response to proteasome stress.
Article
Oncology
Rong Zhao, Yan Liu, Ziwei Wang, Jun Zhang, Wei Zhang, Xing Zhou, Sevjid Tsedendorj, Amarsanaa Enkhtur, Dilu Feng, Hongbo Wang
Summary: Recent studies have found that UBE2C inhibits autophagy and affects the apoptosis and proliferation of endometrial cancer cells. UBE2C induces the ubiquitination and degradation of SIRT1, leading to the epigenetic inhibition of autophagy-related genes. These findings provide new insights into the treatment of endometrial cancer.
MOLECULAR CANCER RESEARCH
(2023)
Article
Clinical Neurology
Xia Liu, Qinlian Ye, Zhengzheng Huang, Xiuping Li, Liping Zhang, Xuan Liu, Yun-Cheng Wu, Ulf Brockmeier, Dirk M. Hermann, Ya-Chao Wang, Lijie Ren
Summary: In this study, a switch from UPS to autophagy due to changes in BAG3 expression was observed in cerebral ischemia. BAG3 overexpression activated autophagy and inhibited apoptosis, leading to improved neurological function and reduced ischemic injury.
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
Oncology
Margot De Marco, Antonia Falco, Roberta Laccarino, Antonio Raffone, Antonio Mono, Maurizio Guida, Alessandra Rosati, Massimiliano Chetta, Giovanni Genovese, Francesco De Caro, Mario Capunzo, Maria Caterina Turco, Vladimir N. Uversky, Liberato Marzullo
Summary: BAG3, a multidomain protein, plays a role in cellular processes such as apoptosis, autophagy, and cytoskeletal dynamics. It has been reported to promote cell survival and resistance to therapy in certain tumors, and its expression is associated with ovarian, endometrial, and cervical cancers. Additionally, the interaction of BAG3 with human papillomavirus proteins may contribute to our understanding of virus-induced oncogenesis.
BRITISH JOURNAL OF CANCER
(2021)
Review
Biochemistry & Molecular Biology
Qinghan Liu, Jinde Liu, Xinyue Huang
Summary: BAG3, a multifunctional protein, participates in major cellular pathways and plays a crucial role in hematological malignancies. Modulation of BAG3 and its corresponding proteins could be a potential target for therapy and experiments. This review provides a reference for further investigations on the characteristics of BAG3 in hematological malignancies.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Review
Medicine, Research & Experimental
Jonathan A. Kirk, Joseph Y. Cheung, Arthur M. Feldman
Summary: BAG3 is a protein that is expressed ubiquitously in humans, with highest levels in the heart, skeletal muscle, and central nervous system, as well as in many cancers. It plays diverse roles in both the heart and cancer cells, including apoptosis inhibition, autophagy promotion, and maintenance of cellular structure. However, targeting BAG3 function in cancer cells may pose challenges due to its essential roles in the heart.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Medical Laboratory Technology
Pengyu Jia, Nan Wu, Huimin Yang, Yuxuan Guo, Xiaofan Guo, Yingxian Sun
Summary: BAG3 protein is highly expressed in the heart and plays a significant role in both physiological hypertrophy and pathological remodeling. Knockout of BAG3 inhibits physiological hypertrophy while exacerbating pathological remodeling, whereas overexpression of BAG3 promotes physiological hypertrophy and inhibits pathological remodeling.
TRANSLATIONAL RESEARCH
(2021)
Article
Oncology
Jie Lu, Shuang-Yu Liu, Jing Zhang, Guang-Ming Yang, Gui-Bin Gao, Nan-Nan Yu, Yan-Ping Li, Yi-Xiang Li, Zhong-Qi Ma, Yang Wang, Chun-Hua Lu
Summary: Shikonin induces nuclear translocation of PKM2 to recruit Nrf2 and activate downstream gene BAG3, enhancing cell survival. Combined with BAG3 inhibitor, shikonin shows promising therapeutic potential for HCC therapy.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Jieyan Wang, Yingling Wang, Shihan He, Zhu Wang, Qiong Deng, Hui Liang
Summary: Inhibition of proteasomes by MG132 leads to macrophage apoptosis by promoting ROS production and mitochondrial dysfunction.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ling-Ling Zhao, Jiao-Na Gu, Xiao-Fang Zhu, Yin Hu, Hong Cao, Na Yao, Hua Sang, Bei-Bei Guo, Yu-Hang Wang, Hong-Yan Qian, Wei-Zhong Zhu
Summary: Despite previous studies confirming the anti-apoptotic effect of Bcl-2 associated athanogene3 (BAG3) in myocardium, the specific structural domains PXXP and BAG responsible for this protection have not been fully understood. Over-expression of BAG3 has been shown to reduce injury induced by hypoxia/reoxygenation in both neonatal and adult rat cardiomyocytes, with PXXP and BAG domains playing a critical role in cellular protection under H/R stress. The results suggest that BAG3's protective effect on apoptosis induced by H/R stress is closely linked to its structural domains PXXP and BAG, pointing towards a potential new therapeutic strategy for ischemic cardiomyopathy.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2021)
Article
Cell Biology
Melanie Op, Sergio T. Ribeiro, Claire Chavarria, Aude De Gassart, Lea Zaffalon, Fabio Martinon
Summary: Proteasome inhibitors like bortezomib are commonly used as first-line therapy for multiple myeloma (MM), but patients often develop resistance to this treatment. This study examines the role of the DDI2-NRF1 pathway in bortezomib resistance. The researchers find that prolonged bortezomib treatment leads to increased expression of DDI2 and activation of NRF1, resulting in resistance to proteasome inhibition. They also demonstrate that MM cells with DDI2 deficiency are more sensitive to proteasome impairment. Furthermore, partial inhibition of the DDI2 protease domain with nelfinavir enhances bortezomib susceptibility in MM cells. These findings highlight the importance of the DDI2-NRF1 pathway in proteasome inhibition responses and identify potential targets for bortezomib-treated MM patients.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Radek Jorda, Veronika Molitorova, Eliska Pilarova, Veronika Vojackova, Eva Reznickova, Klara Svobodova, Karel Pauk, Ales Imramovsky, Vladimir Krystof
Summary: The comparative study examined new proteasome inhibitors based on salicylic acid-modified pseudo-tripeptides with aldehyde or vinylsulfone terminations. The study found that aldehydes were more effective than vinylsulfones in inhibiting proteasomes in cells, inducing the accumulation of polyubiquitinated proteins, GFP accumulation, and apoptotic cell death.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ethan L. L. Morgan, Tiffany Toni, Ramya Viswanathan, Yvette Robbins, Xinping Yang, Hui Cheng, Sreenivasulu Gunti, Angel Huynh, Anastasia L. L. Sowers, James B. B. Mitchell, Clint T. T. Allen, Zhong Chen, Carter Van Waes
Summary: TNF alpha is a key mediator of immune, chemotherapy and radiotherapy-induced cytotoxicity, but several cancers display resistance to TNF alpha due to activation of the NF kappa B pro-survival pathway. In this study, we found that the expression of USP14, a proteasome-associated deubiquitinase, is increased in HNSCC and correlates with worse progression free survival. Inhibition or depletion of USP14 inhibited the proliferation and survival of HNSCC cells and reduced NF kappa B activity. Furthermore, we showed that the inhibitor b-AP15 sensitized HNSCC cells to TNF alpha-mediated cell death and radiation-induced cell death, and delayed tumor growth in vivo.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Biotechnology & Applied Microbiology
Zhong Chu, Nan Huo, Xiang Zhu, Hanxiao Liu, Rui Cong, Luyuan Ma, Xiaofeng Kang, Chunyuan Xue, Jingtong Li, Qihong Li, Hua You, Qingyuan Zhang, Xiaojie Xu
Summary: The study identified a lncRNA called LINC00926 that negatively regulates PGK1 expression and predicts good clinical outcomes in breast cancer. Hypoxia inhibits LINC00926 expression and activates PGK1 expression through FOXO3A. This discovery established FOXO3A/LINC00926/PGK1 as a critical axis in regulating breast cancer growth and progression.
Article
Biochemistry & Molecular Biology
Soojung Hahn, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim
Summary: This study utilized three-dimensional intestinal organoids to investigate the effects of metformin on inflammatory bowel disease (IBD) and found that metformin can enhance intestinal barrier function and reduce levels of inflammatory cytokines.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
V. V. Sudarev, M. S. Gette, S. V. Bazhenov, O. M. Tilinova, E. V. Zinovev, I. V. Manukhov, A. I. Kuklin, Yu. L. Ryzhykau, A. V. Vlasov
Summary: This study investigated the self-assembly processes of ferritin-based protein complexes and obtained structurally characterized oligomeric states. These results provide new potential and opportunities for the application of ferritin in various fields.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Yalda Sabaghi, Farnaz Pourfarzad, Leila Zolghadr, Azita Bahrami, Tahereh Shojazadeh, Alireza Farasat, Nematollah Gheibi
Summary: p-Coumaric acid (p-CA) is a plant compound with anti-cancer activities. This study designed a nano-liposomal carrier containing p-CA to enhance its effectiveness against melanoma cells. The findings showed that the liposomal form of p-CA had a greater impact on the cells. Kinetic modeling indicated that the best fitting model was zero-order.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
M. D. Nazmul Hasan, Md Mahfuzur Rahman, Al Asmaul Husna, Nobuhiro Nozaki, Osamu Yamato, Naoki Miura
Summary: This study investigated the expression of ncRNAs other than miRNAs in different histologic subtypes of canine mammary gland tumors (MGT). Three aberrantly expressed ncRNAs were identified as potential biomarkers for differentiating MGT subtypes. YRNA and tRFs expression levels were found to be decreased in metastatic compared to primary MGT cell lines.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Seine A. Shintani
Summary: In this study, the researchers used signal analysis to study the instantaneous amplitude and phase of sarcomeric oscillations in skeletal muscle. They identified two types of oscillations, sarcomeric oscillations and sarcosynced oscillations, and visualized their behavior during propagating waves. The researchers discovered the presence of sarcomeric defect holes and sarcomeric collision holes, which are important indicators for understanding the oscillation properties of sarcomeres. This finding has important implications for improving our understanding of muscle function and its regulatory mechanisms.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Shuanglin Zhang, Yuzhong Jia, Guolan Ma, Yanyan Yang, Zhenzhen Cao, Antao Luo, Zefu Zhang, Shihan Li, Jie Wen, Hanfeng Liu, Jihua Ma
Summary: Bupleurum is an antiarrhythmic agent that may exert its effects by inhibiting L-type calcium channels.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Tomotaka Ohkubo, Yasuhiko Matsumoto, Hiroaki Sasaki, Kaoru Kinoshita, Yuki Ogasawara, Takashi Sugita
Summary: This study found that Citrobacter koseri inhibits the growth of Staphylococcus epidermidis, disrupting the balance between S. epidermidis and Staphylococcus aureus, and exacerbating inflammation in atopic dermatitis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Toshifumi Asano, Philipp Sasse, Takao Nakata
Summary: A Cre recombination-based fluorescent reporter system was developed to monitor cell-cell fusion. The system successfully detected the formation of multinuclear myotubes and placental syncytiotrophoblast. This tool could facilitate the study of cell-to-cell fusion.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Ke Shi, Yunlong Shan, Xiao Sun, Kuida Chen, Qiong Luo, Qiang Xu
Summary: This study found that low expression of TP53INP2 is associated with poor survival in colorectal cancer (CRC) patients. As the malignancy of CRC progresses, TP53INP2 expression gradually decreases. Knockdown of TP53INP2 promotes CRC cell proliferation and tumor growth. Mechanistically, TP53INP2 deficiency decreases phosphorylation of beta-catenin, leading to increased accumulation and enhanced nuclear translocation and transcriptional activity. Additionally, TP53INP2 sequesters TIM50, inhibiting its activation of beta-catenin. In conclusion, downregulation of TP53INP2 promotes CRC progression by activating beta-catenin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Martina Rossi, Fabio Tomaselli, Alejandro Hochkoeppler
Summary: Oligomeric enzymes are known for their higher catalytic rates compared to monomeric enzymes, but the extent of additivity in their activity is still not well understood. This study used tetrameric rabbit lactate dehydrogenase as a model to examine the kinetics of its catalytic action. Surprisingly, when the concentration of the limiting reactant exceeded that of a single subunit, there was a significant slowdown in the enzyme's conformational rearrangements.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Amin Sahraei, Mohammad Javad Shamsoddini, Fakhrossadat Mohammadi, Leila Hassani
Summary: This study explored the inhibitory effects of gallium curcumin, indium curcumin, and vanadyl curcumin on the amyloid fibrillation of hen egg white lysozyme, as well as the binding interactions of these metal complexes with the enzyme. The results showed that indium curcumin and vanadyl curcumin exhibited higher binding affinities and stronger inhibitory effects on amyloid fibrillation compared to gallium curcumin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Takahiro Sasaki, Yoshiki Kuse, Shinsuke Nakamura, Masamitsu Shimazawa
Summary: PGRN deficiency plays a significant role in cardiac remodeling and arrhythmias post-myocardial infarction (MI), potentially by promoting metabolic abnormalities in macrophages.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Hongwei Zhao, Yiqiang Li, Yibo Zhang, Chi Zhang
Summary: Electrical brain stimulation technology is commonly used to treat brain neurological disorders, but it can cause side effects. This study investigated the impact of electric fields on nerve fibers and revealed the possible origin of side effects. The findings provide guidance for selecting electrical parameters in clinical stimulation therapy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Julia S. Scott, Lake-Ee Quek, Andrew J. Hoy, Johannes V. Swinnen, Zeyad D. Nassar, Lisa M. Butler
Summary: The fatty acid elongation enzyme ELOVL5 plays a critical role in promoting metastasis in prostate cancer. Knocking down ELOVL5 leads to the accumulation of malonyl-CoA, which inhibits fatty acid oxidation in mitochondria. This study highlights the importance of fatty acid elongation in regulating cell viability and provides a potential target for prostate cancer treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Zan Zhou, Wen-jun Jiang, Li Li, Jun-qiang Si
Summary: This study investigates the effect of noise exposure on cognitive function in mice and explores the underlying molecular mechanisms. The findings suggest that noise exposure leads to increased inflammation, increased phosphorylation of Tau protein, and decreased levels of postsynaptic density protein, resulting in cognitive impairment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)