title: UXT plays dual opposing roles on SARM-induced apoptosis.
abstract: Apoptosis is a vital defense mechanism for the clearance of infected cells. Ubiquitously expressed transcript (UXT), which exists in two isoforms (V1 and V2), interact with both apoptotic and cellular proteins. By yeast two-hybrid analysis, we found that UXT interacts with SARM (sterile α and HEAT armadillo motif-containing protein). Since SARM is a TLR adaptor which induces intrinsic apoptosis following immune activation, we were prompted to query whether UXT and SARM might co-regulate apoptosis. We found that the UXT isoforms elicit dual opposing regulatory effects on SARM-induced apoptosis; while UXT V1, co-expressed with SARM, caused a reduction in caspase 8 activity, UXT V2 strongly increased caspase 8 activity and enhanced SARM-induced apoptosis by activating the extrinsic pathway and depolarizing the mitochondria.
authors.affiliation: Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Shalini
authors.initials: S
authors.lastname: Sethurathinam
authors.forename: Laishram Pradeepkumar
authors.initials: LP
authors.lastname: Singh
authors.forename: Porkodi
authors.initials: P
authors.lastname: Panneerselvam
authors.forename: Bernadette
authors.initials: B
authors.lastname: Byrne
authors.forename: Jeak Ling
authors.initials: JL
authors.lastname: Ding
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D051186:Armadillo Domain Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D002460:Cell Line; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D051186:Armadillo Domain Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D020033:Protein Isoforms; C435689:SARM1 protein, human; C118920:UXT protein, human
keywords: Apoptosis; FADD; FAS associated protein with death domain; Infection-inflammation condition; LPS; MAVS; Mitochondrial depolarization; SARM; Sterile α and HEAT armadillo motif-containing protein (SARM); TIR; TLR; TMRE; TNF; TNF receptor associated death domain; TNF receptor–associated factor 2; TRADD; TRAF2; UXT; Ubiquitously expressed transcript (UXT); lipopolysaccharide; mitochondrial anti-viral signaling protein; sterile α and heat armadillo motif-containing protein; tetramethylrhodamine ethyl ester perchlorate; toll-like receptor; toll/interleukin-1 receptor; tumor necrosis factor; ubiquitously expressed transcript