title: JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress.
abstract: c-myc and p53 networks control proliferation, differentiation, and apoptosis and are responsive to, and cross-regulate a variety of stresses and metabolic and biosynthetic processes. At c-myc, the far upstream element binding protein (FBP) and FBP-interacting repressor (FIR) program transcription by looping to RNA polymerase II complexes engaged at the promoter. Another FBP partner, JTV1/AIMP2, a structural subunit of a multi-aminoacyl-tRNA synthetase (ARS) complex, has also been reported to stabilize p53 via an apparently independent mechanism. Here, we show that in response to oxidative stress, JTV1 dissociates from the ARS complex, translocates to the nucleus, associates with FBP and co-activates the transcription of a new FBP target, ubiquitin-specific peptidase 29 (USP29). A previously uncharacterized deubiquitinating enzyme, USP29 binds to, cleaves poly-ubiquitin chains from, and stabilizes p53. The accumulated p53 quickly induces apoptosis. Thus, FBP and JTV1 help to coordinate the molecular and cellular response to oxidative stress.
authors.affiliation: Gene Regulation Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA. juhong.liu@fda.hhs.gov
authors.forename: Juhong
authors.initials: J
authors.lastname: Liu
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Chung
authors.forename: Matthew
authors.initials: M
authors.lastname: Vogt
authors.forename: Yetao
authors.initials: Y
authors.lastname: Jin
authors.forename: Daniela
authors.initials: D
authors.lastname: Malide
authors.forename: Liusheng
authors.initials: L
authors.lastname: He
authors.forename: Miroslav
authors.initials: M
authors.lastname: Dundr
authors.forename: David
authors.initials: D
authors.lastname: Levens
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins; D012045:Regulatory Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; C492258:FUBP1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; C474321:aminoacyl-tRNA synthetase-associated protein p38; D008156:Luciferases; D010450:Endopeptidases; C579223:USP29 protein, human; D064570:Ubiquitin-Specific Proteases; D004265:DNA Helicases; D000604:Amino Acyl-tRNA Synthetases