JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress

• Published in: The EMBO journal Vol. 30; no. 5; pp. 846 - 858
• Main Authors: Liu, Juhong, Chung, Hye-Jung, Vogt, Matthew, Jin, Yetao, Malide, Daniela, He, Liusheng, Dundr, Miroslav, Levens, David
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 02.03.2011; Nature Publishing Group UK; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Amino Acyl-tRNA Synthetases - genetics; Amino Acyl-tRNA Synthetases - metabolism; Apoptosis; Biomarkers - metabolism; Blotting, Western; Cell Nucleus - genetics; Cell Nucleus - metabolism; DNA Helicases - genetics; DNA Helicases - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Electrophoretic Mobility Shift Assay; Endopeptidases - genetics; Endopeptidases - metabolism; FBP; Flow Cytometry; Gene expression; Gene Expression Profiling; Humans; Immunoenzyme Techniques; JTV1; Luciferases - metabolism; Molecular biology; Oligonucleotide Array Sequence Analysis; Oxidative Stress; p53; Promoter Regions, Genetic; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Regulatory Sequences, Nucleic Acid; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Signal transduction; Tumor Suppressor Protein p53 - chemistry; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Ubiquitin - metabolism; Ubiquitin-Specific Proteases; USP29; apoptosis; FBP; USP29; JTV1; p53
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2011.11

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. USP29 joins the family of deubiquitinating enzymes involved in the stabilization of p53. Furthermore, p53 regulation is in this case linked to the c‐Myc pathway, whose constituents JTV1 and FBP control USP29 expression upon oxidative stress.