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Myrf is a newly discovered membrane-bound transcription factor that plays an essential role in as diverse organisms as human, worm, and slime mold. Myrf is generated as a type-II membrane protein in the endoplasmic reticulum (ER). It forms homo-oligomers to undergo auto-cleavage that releases Myrf N-terminal fragment from the ER membrane as a homo-trimer. The homo-trimer of Myrf N-terminal fragments enters the nucleus and binds the Myrf motif to activate transcription. Despite its prominent role as a transcriptional activator, little is known about the transactivation domain of Myrf. Here, we report that the N-terminal-most (NTM) domain of Myrf is required for transcriptional activity and, when fused to a Gal4 fragment, enables it to activate transcription. The transactivation function of the NTM domain did not require homo-trimerization. We also discovered that the NTM domain can be sumoylated at three lysine residues (K123, K208, and K276), with K276 serving as the main acceptor. K276 sumoylation repressed the transactivation function of the NTM domain without affecting the stability or nuclear localization of Myrf N-terminal fragment. In sum, this study identifies the NTM domain as the transactivation domain of Myrf and the potential regulatory impact of its K276 sumoylation.
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http://dx.doi.org/10.1038/s41598-018-31477-4 | DOI Listing |
J Trauma Acute Care Surg
August 2025
From the Division of Acute Care Surgery (S.F., J.J.D.), Department of Surgery, Morsani College of Medicine, University of South Florida; Program in Trauma (M.H.G.), University of Maryland School of Medicine/R Adams Cowley Shock Trauma Center; University of Texas Southwestern Medical Center (B.B.); a
Abstract: The open abdomen is a heroic surgical technique used in trauma, emergency general surgery, and vascular emergencies. Much has been written about the surgical technique, indications, management, temporizing abdominal closure, and final primary fascial closure. As with all surgical procedures, the open abdomen has associated morbidity and mortality.
View Article and Find Full Text PDFbioRxiv
July 2025
Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Synaptic plasticity in the central nervous system enables the encoding, storing, and integrating new information. AMPA-type glutamate receptors (AMPARs) are ligand-gated ion channels that mediate most fast excitatory synaptic transmission in the brain, and plasticity of AMPARs signaling underlies the long-lasting changes in synaptic efficacy and strength important for learning and memory. Recent work has indicated that the enigmatic N-terminal domain (NTD) of AMPARs may be a critical regulator of synaptic targeting and plasticity of AMPARs.
View Article and Find Full Text PDFInflamm Res
July 2025
Clinical and Research Center for Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
Objective: To investigate the association of genetic polymorphisms in MB21D1 (Mab-21 domain-containing 1), TMEM173 (Transmembrane Protein 173), IFNB1 (Interferon beta 1), IFNGR1 (Interferon gamma receptor 1), IFNGR2 (Interferon gamma receptor 2), IRF3 (Interferon Regulatory Factor 3), and IRF8 (Interferon Regulatory Factor 8) with susceptibility to non-tuberculous mycobacteria pulmonary disease (NTM-PD) as well as their correlation with the treatment outcomes and immune status of patients.
Methods: Forty-four tagSNPs from the candidate genes were genotyped in a 2-phase cohort study including an initial discovery phase involving 707 NTM-PD patients and 726 healthy controls and a replication phase involving 357 NTM-PD patients and 400 controls. The frequencies and distributions of genotypes were compared between the case and control groups.
ACS Infect Dis
May 2025
Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551, Singapore.
The nontuberculous mycobacterium (NTM) () has emerged as a global health concern due to its high intrinsic resistance toward antibiotics. The search for anti-NTM inhibitors requires novel well-characterized targets. The cytochrome (cyt-) oxidase, which serves as an alternate terminal oxidase in mycobacteria, is a chemically validated drug target in .
View Article and Find Full Text PDFMicroorganisms
February 2025
Department of Cell and Molecular Biology, Biomedical Centre, Box 596, SE-751 24 Uppsala, Sweden.
Changes in cell shape have been shown to be an integral part of the mycobacterial life cycle; however, systematic investigations into its patterns of pleomorphic behaviour in connection with stages or conditions of growth are scarce. We have studied the complete growth cycle of cultures, a Non-Tuberculous Mycobacterium (NTM), in solid as well as in liquid media. We provide data showing changes in cell shape from rod to coccoid and occurrence of refractive cells ranging from Phase Grey to phase Bright (PGB) in appearance upon ageing.
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