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JOURNAL ARTICLE
Sean R Corcoran, James D Phelan, Jaewoo Choi, Galina Shevchenko, Rachel E Fenner, Xin Yu, Sebastian Scheich, Tony Hsiao, Vivian M Morris, Evangelia K Papachristou, Kamal Kishore, Clive S D'Santos, Yanlong Ji, Stefania Pittaluga, George W Wright, Henning Urlaub, Kuan-Ting Pan, Thomas Oellerich, Jagan Muppidi, Daniel J Hodson, Louis M Staudt
Polatuzumab Vedotin (Pola-V) is an antibody-drug conjugate directed to the CD79B subunit of the B cell receptor (BCR). When combined with conventional immunochemotherapy, Pola-V improves outcomes in DLBCL. To identify determinants of Pola-V sensitivity, we used CRISPR-Cas9 screening for genes that modulated Pola-V toxicity for lymphomas or the surface expression of its target, CD79B. Our results reveal the striking impact of CD79B glycosylation on Pola-V epitope availability on the lymphoma cell surface and on Pola-V toxicity...
April 25, 2024: Cancer Discovery
#2
JOURNAL ARTICLE
Jiangtao Pu, Dengguo Zhang, Biao Wang, Peiquan Zhu, Wenxing Yang, Kaiqiang Wang, Ze Yang, Qi Song
BACKGROUND: Immune escape is a key factor influencing survival rate of lung adenocarcinoma (LUAD) patients, but molecular mechanism of ubiquitin binding enzyme E2T (UBE2T) affecting immune escape of LUAD remains unclear. The objective was to probe role of UBE2T in LUAD. METHODS: Bioinformatics means were adopted for analyzing UBE2T and forkhead box A1 (FOXA1) expression in LUAD tissues, the gene binding sites, the pathway UBE2T regulates, and the correlation between UBE2T and glycolysis genes...
April 1, 2024: Frontiers in Bioscience (Landmark Edition)
#3
JOURNAL ARTICLE
Binbin Luo, Linyi Song, Limiao Chen, Yue Cai, Mingwei Zhang, Shenyi Wang
BACKGROUND: Gemcitabine (GEM) resistance is the primary reason why combination chemotherapy is limited in triple-negative breast cancer (TNBC). Ganoderic acid D (GAD), a natural triterpenoid compound obtained from Ganoderma lucidum, has been shown to have antitumor activities. However, whether GAD can reverse GEM resistance in TNBC requires further investigation. PURPOSE: This study investigated whether and how GAD could reverse GEM resistance in TNBC as an antitumor adjuvant...
April 23, 2024: Phytomedicine
#4
JOURNAL ARTICLE
Davy Vanhoutte, Tobias G Schips, Rachel A Minerath, Jiuzhou Huo, Naga Swathi Sree Kavuri, Vikram Prasad, Suh-Chin Lin, Michael J Bround, Michelle A Sargent, Christopher M Adams, Jeffery D Molkentin
Loss of muscle mass is a feature of chronic illness and aging. Here, we report that skeletal muscle-specific thrombospondin-1 transgenic mice (Thbs1 Tg) have profound muscle atrophy with age-dependent decreases in exercise capacity and premature lethality. Mechanistically, Thbs1 activates transforming growth factor β (TGFβ)-Smad2/3 signaling, which also induces activating transcription factor 4 (ATF4) expression that together modulates the autophagy-lysosomal pathway (ALP) and ubiquitin-proteasome system (UPS) to facilitate muscle atrophy...
April 26, 2024: Cell Reports
#5
JOURNAL ARTICLE
Akiko Yamamuro-Tanabe, Yu Oshima, Takumi Iyama, Yuki Ishimaru, Yasuhiro Yoshioka
The ubiquitin-proteasome system (UPS) is a major proteolytic system that plays an important role in the regulation of various cell processes, such as cell cycle, stress response, and transcriptional regulation, especially in neurons, and dysfunction of UPS is considered to be a cause of neuronal cell death in neurodegenerative diseases. However, the mechanism of neuronal cell death caused by UPS dysfunction has not yet been fully elucidated. In this study, we investigated the mechanism of neuronal cell death induced by proteasome inhibitors using human neuroblastoma SH-SY5Y cells...
June 2024: Journal of Pharmacological Sciences
#6
JOURNAL ARTICLE
Weixi Xie, Lang Deng, Rui Qian, Xiaoting Huang, Wei Liu, Siyuan Tang
The senescence of alveolar epithelial cells (AECs) and fibroblasts plays a pivotal role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a condition lacking specific therapeutic interventions. Curculigoside (CCG), a prominent bioactive constituent of Curculigo , exhibits anti-osteoporotic and antioxidant activities. Our investigation aimed to elucidate the anti-senescence and anti-fibrotic effects of CCG in experimental pulmonary fibrosis and delineate its underlying molecular mechanisms. Our findings demonstrate that CCG attenuates bleomycin-induced pulmonary fibrosis and lung senescence in murine models, concomitantly ameliorating lung function impairment...
March 29, 2024: Antioxidants (Basel, Switzerland)
#7
JOURNAL ARTICLE
Yajiao Pang, Hongrong Wang, Qiaoyi Xie, Tingting Ma
BACKGROUND: Pneumonia is a prevalent respiratory ailment involving complex physiological and pathological mechanisms. The tripartite motif containing 27 (TRIM27) plays a crucial role in regulating inflammation mechanisms. Therefore, the purpose of this study is to further explore the therapeutic potential of TRIM27 in pneumonia, based on its regulatory mechanisms in inflammation and autophagy. METHODS: This study established a mouse pneumonia animal model through lipopolysaccharide (LPS) administration, designating it as the LPS model group...
April 2024: Discovery Medicine
#8
JOURNAL ARTICLE
Fabian Offensperger, Gary Tin, Miquel Duran-Frigola, Elisa Hahn, Sarah Dobner, Christopher W Am Ende, Joseph W Strohbach, Andrea Rukavina, Vincenth Brennsteiner, Kevin Ogilvie, Nara Marella, Katharina Kladnik, Rodolfo Ciuffa, Jaimeen D Majmudar, S Denise Field, Ariel Bensimon, Luca Ferrari, Evandro Ferrada, Amanda Ng, Zhechun Zhang, Gianluca Degliesposti, Andras Boeszoermenyi, Sascha Martens, Robert Stanton, André C Müller, J Thomas Hannich, David Hepworth, Giulio Superti-Furga, Stefan Kubicek, Monica Schenone, Georg E Winter
Chemical modulation of proteins enables a mechanistic understanding of biology and represents the foundation of most therapeutics. However, despite decades of research, 80% of the human proteome lacks functional ligands. Chemical proteomics has advanced fragment-based ligand discovery toward cellular systems, but throughput limitations have stymied the scalable identification of fragment-protein interactions. We report proteome-wide maps of protein-binding propensity for 407 structurally diverse small-molecule fragments...
April 26, 2024: Science
#9
JOURNAL ARTICLE
Maíra C Scarpelli, João G A Bergamasco, Joshua S Godwin, Paulo H C Mesquita, Talisson S Chaves, Deivid G Silva, Diego Bittencourt, Nathalia F Dias, Ricardo A Medalha Junior, Paulo C Carello Filho, Vitor Angleri, Luiz A R Costa, Andreas N Kavazis, Carlos Ugrinowitsch, Michael D Roberts, Cleiton A Libardi
PURPOSE: Resistance training (RT) induces muscle growth at varying rates across RT phases, and evidence suggests that the muscle-molecular responses to training bouts become refined or attenuated in the trained state. This study examined how proteolysis-related biomarkers and extracellular matrix (ECM) remodeling factors respond to a bout of RT in the untrained (UT) and trained (T) state. METHODS: Participants (19 women and 19 men) underwent 10 weeks of RT...
April 23, 2024: European Journal of Applied Physiology
#10
JOURNAL ARTICLE
Michael D Roberts, Bradley A Ruple, Joshua S Godwin, Mason C McIntosh, Shao-Yung Chen, Nicholas J Kontos, Anthony Agyin-Birikorang, Max Michel, Daniel L Plotkin, Madison L Mattingly, Brooks Mobley, Tim N Ziegenfuss, Andrew D Fruge, Andreas N Kavazis
The skeletal muscle proteome alterations to aging and resistance training have been reported in prior studies. However, conventional proteomics in skeletal muscle typically yields wide protein abundance ranges that mask the detection of lowly expressed proteins. Thus, we adopted a novel deep proteomics approach whereby myofibril (MyoF) and non-MyoF fractions were separately subjected to protein corona nanoparticle complex formation prior to digestion and Liquid Chromatography Mass Spectrometry (LC-MS). Specifically, we investigated MyoF and non-MyoF proteomic profiles of the vastus lateralis muscle of younger (Y, 22±2 years old; n=5) and middle-aged participants (MA, 56±8 years old; n=6)...
April 19, 2024: Aging
#11
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
April 19, 2024: Science
#12
JOURNAL ARTICLE
Sung Won Cho, Jameela Lokhandwala, Jun Sang Park, Hye Won Kang, Mingi Choi, Hong-Quan Yang, Takato Imaizumi, Brian D Zoltowski, Young Hun Song
FKF1 dimerization is crucial for proper FT levels to fine-tune flowering time. Attenuating FKF1 homodimerization increased CO abundance by enhancing its COP1 binding, thereby accelerating flowering under long days. In Arabidopsis (Arabidopsis thaliana), the blue-light photoreceptor FKF1 (FLAVIN-BINDING, KELCH REPEAT, F-BOX 1) plays a key role in inducing the expression of FLOWERING LOCUS T (FT), encoding the main florigenic signal in plants, in the late afternoon under long-day conditions (LDs) by forming dimers with FT regulators...
April 18, 2024: Plant Cell Reports
#13
JOURNAL ARTICLE
Veronica Jové, Heather Wheeler, Chiachin Wilson Lee, David R Healy, Kymberly Levine, Erik C Ralph, Masaya Yamaguchi, Ziyue Karen Jiang, Edward Cabral, Yingrong Xu, Jeffrey Stock, Bing Yang, Anand Giddabasappa, Paula Loria, Agustin Casimiro-Garcia, Benedikt M Kessler, Adán Pinto-Fernández, Véronique Frattini, Paul D Wes, Feng Wang
Precise regulation of Type I interferon signaling is crucial for combating infection and cancer while avoiding autoimmunity. Type I interferon signaling is negatively regulated by USP18. USP18 cleaves ISG15, an interferon-induced ubiquitin-like modification, via its canonical catalytic function, and inhibits Type I interferon receptor activity through its scaffold role. USP18 loss-of-function dramatically impacts immune regulation, pathogen susceptibility, and tumor growth. However, prior studies have reached conflicting conclusions regarding the relative importance of catalytic versus scaffold function...
April 19, 2024: IScience
#14
JOURNAL ARTICLE
Muthita Hirunsai, Ratchakrit Srikuea
Renin-angiotensin system activation contributes to skeletal muscle atrophy in aging individuals with chronic diseases. We aimed to explore the effects of cholecalciferol (VD3 ) and calcitriol (1,25VD3 ) on signaling of muscle proteolysis and oxidative stress in myotubes challenged with angiotensin II (AII). The mouse C2C12 myotubes were assigned to vehicle, AII, AII + VD3 , AII + 1,25VD3 , and AII + losartan groups. The expression levels of muscle-specific E3 ubiquitin ligase proteins, autophagy-related proteins, and oxidative stress markers were investigated...
April 2024: Physiological Reports
#15
JOURNAL ARTICLE
Hirotsugu Oda, Kalpana Manthiram, Pallavi Pimpale Chavan, Eva Rieser, Önay Veli, Öykü Kaya, Charles Rauch, Shuichiro Nakabo, Hye Sun Kuehn, Mariël Swart, Yanli Wang, Nisa Ilgim Çelik, Anne Molitor, Vahid Ziaee, Nasim Movahedi, Mohammad Shahrooei, Nima Parvaneh, Nasrin Alipour-Olyei, Raphael Carapito, Qin Xu, Silvia Preite, David B Beck, Jae Jin Chae, Michele Nehrebecky, Amanda K Ombrello, Patrycja Hoffmann, Tina Romeo, Natalie T Deuitch, Brynja Matthíasardóttir, James Mullikin, Hirsh Komarow, Jennifer Stoddard, Julie Niemela, Kerry Dobbs, Colin L Sweeney, Holly Anderton, Kate E Lawlor, Hiroyuki Yoshitomi, Dan Yang, Manfred Boehm, Jeremy Davis, Pamela Mudd, Davide Randazzo, Wanxia Li Tsai, Massimo Gadina, Mariana J Kaplan, Junya Toguchida, Christian T Mayer, Sergio D Rosenzweig, Luigi D Notarangelo, Kazuhiro Iwai, John Silke, Pamela L Schwartzberg, Bertrand Boisson, Jean-Laurent Casanova, Seiamak Bahram, Anand Prahalad Rao, Nieves Peltzer, Henning Walczak, Najoua Lalaoui, Ivona Aksentijevich, Daniel L Kastner
The linear ubiquitin assembly complex (LUBAC) consists of HOIP, HOIL-1 and SHARPIN and is essential for proper immune responses. Individuals with HOIP and HOIL-1 deficiencies present with severe immunodeficiency, autoinflammation and glycogen storage disease. In mice, the loss of Sharpin leads to severe dermatitis due to excessive keratinocyte cell death. Here, we report two individuals with SHARPIN deficiency who manifest autoinflammatory symptoms but unexpectedly no dermatological problems. Fibroblasts and B cells from these individuals showed attenuated canonical NF-κB responses and a propensity for cell death mediated by TNF superfamily members...
April 12, 2024: Nature Immunology
#16
JOURNAL ARTICLE
Daniel Horn-Ghetko, Linus V M Hopf, Ishita Tripathi-Giesgen, Jiale Du, Sebastian Kostrhon, D Tung Vu, Viola Beier, Barbara Steigenberger, J Rajan Prabu, Luca Stier, Elias M Bruss, Matthias Mann, Yue Xiong, Brenda A Schulman
Ubiquitin ligation is typically executed by hallmark E3 catalytic domains. Two such domains, 'cullin-RING' and 'RBR', are individually found in several hundred human E3 ligases, and collaborate with E2 enzymes to catalyze ubiquitylation. However, the vertebrate-specific CUL9 complex with RBX1 (also called ROC1), of interest due to its tumor suppressive interaction with TP53, uniquely encompasses both cullin-RING and RBR domains. Here, cryo-EM, biochemistry and cellular assays elucidate a 1.8-MDa hexameric human CUL9-RBX1 assembly...
April 11, 2024: Nature Structural & Molecular Biology
#17
JOURNAL ARTICLE
Jinyuan Xu, Lilin Zhu, Jie Xu, Kailong Lin, Juan Wang, Yan-Long Bi, Guo-Tong Xu, Haibin Tian, Furong Gao, Caixia Jin, Lixia Lu
BACKGROUND: To identify key and shared insulin resistance (IR) molecular signatures across all insulin-sensitive tissues (ISTs), and their potential targeted drugs. METHODS: Three datasets from Gene Expression Omnibus (GEO) were acquired, in which the ISTs (fat, muscle, and liver) were from the same individual with obese mice. Integrated bioinformatics analysis was performed to obtain the differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was carried out to determine the "most significant trait-related genes" (MSTRGs)...
2024: Frontiers in Nutrition
#18
JOURNAL ARTICLE
D García-Gomis, J López, A Calderón, M Andrés, I Ponte, A Roque
Histone H1 is involved in chromatin compaction and dynamics. In human cells, the H1 complement is formed by different amounts of somatic H1 subtypes, H1.0-H1.5 and H1X. The amount of each variant depends on the cell type, the cell cycle phase, and the time of development and can be altered in disease. However, the mechanisms regulating H1 protein levels have not been described. We have analyzed the contribution of the proteasome to the degradation of H1 subtypes in human cells using two different inhibitors: MG132 and bortezomib...
May 2024: Protein Science
#19
JOURNAL ARTICLE
Alexander V Skurat, Dyann M Segvich, Christopher J Contreras, Yueh-Chiang Hu, Thomas D Hurley, Anna A DePaoli-Roach, Peter J Roach
Lafora disease (LD) is an autosomal recessive myoclonus epilepsy with onset in the teenage years leading to death within a decade of onset. LD is characterized by the overaccumulation of hyperphosphorylated, poorly branched, insoluble, glycogen-like polymers called Lafora bodies. The disease is caused by mutations in either EPM2A, encoding laforin, a dual specificity phosphatase that dephosphorylates glycogen, or EMP2B, encoding malin, an E3-ubiquitin ligase. While glycogen is a widely accepted laforin substrate, substrates for malin have been difficult to identify partly due to the lack of malin antibodies able to detect malin in vivo...
April 6, 2024: Journal of Biological Chemistry
#20
JOURNAL ARTICLE
Ehrlichia chaffeensis TRP120 ubiquitinates tumor suppressor APC to modulate Hippo and Wnt signaling.
Caitlan D Byerly, Bing Zhu, Paityn A Warwick, LaNisha L Patterson, Nicholas A Pittner, Jere W McBride
Ehrlichia chaffeensis: TRP120 is a multifunctional effector that acts as a ligand mimic to activate evolutionary conserved eukaryotic signaling pathways Notch, Wnt, Hedgehog and Hippo. In addition, TRP120 is also a HECT E3 ubiquitin ligase known to ubiquitinate several host cell regulatory proteins (FBW7, PCGF5 and ENO-1) for degradation. We previously determined that TRP120 ubiquitinates the Notch negative regulator, FBW7, to maintain Notch signaling and promote infection. In this study, we investigated a potential mechanism used by Ehrlichia chaffeensis to maintain Hippo and Wnt signaling by ubiquitinating the tumor suppressor, adenomatous polyposis coli (APC), a negative regulator of Wnt and Hippo signaling...
2024: Frontiers in Cell and Developmental Biology
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