JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress
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 b...
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Published in | The EMBO journal Vol. 30; no. 5; pp. 846 - 858 |
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Main Authors | , , , , , , , |
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 | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ark:/67375/WNG-4D4MRJTH-Q ArticleID:EMBJ201111 istex:1C0A10E54AACFCCDEA943BFF71B846BB76D67F7B Supplementary DataReview Process File ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 |
ISSN: | 0261-4189 1460-2075 |
DOI: | 10.1038/emboj.2011.11 |