Document Detail

The antiapoptotic DeltaNp73 is degraded in a c-Jun-dependent manner upon genotoxic stress through the antizyme-mediated pathway.
MedLine Citation:
PMID:  20185758     Owner:  NLM     Status:  MEDLINE    
p73, the structural and functional homologue of p53, exists as two major forms: the transactivation-proficient, proapoptotic TAp73 or the transactivation-deficient, antiapoptotic DNp73. Expectedly, expression of both these major forms has to be coordinated precisely to achieve the desired cellular outcome. Genotoxic insults resulting in cell death lead to the stabilization of TAp73, mainly through posttranslational modifications, and the concomitant degradation of DNp73, through poorly understood mechanisms. We have therefore investigated the possible mechanisms of stress-induced DNp73 degradation and show here that c-Jun, the AP-1 family member activated by stress signals and involved in stabilizing TAp73, promotes DNp73 degradation. Genotoxic stress-mediated DNp73 degradation was found to occur in a c-Jun-dependent manner through a ubiquitin-independent but proteasome-dependent mechanism. Absence or down-regulation of c-Jun expression abrogated the reduction of DNp73 levels upon stress insults, whereas overexpression of c-Jun led to its degradation. c-Jun controlled DNp73 degradation through the nonclassical, polyamine-induced antizyme (Az) pathway by regulating the latter's processing during stress response. Consistently, expression of c-Jun or Az, or addition of polyamines, promoted DNp73 degradation, whereas silencing Az expression or inhibiting Az activity in cells exposed to stress reduced c-Jun-dependent DNp73 degradation. Moreover, Az was able to bind to DNp73. These data together demonstrate the existence of a c-Jun-dependent mechanism regulating the abundance of the antiapoptotic DNp73 in response to genotoxic stress.
Iqbal Dulloo; Ganesan Gopalan; Gerry Melino; Kanaga Sabapathy
Related Documents :
8319568 - Estrogen induces expression of c-jun and jun-b protooncogenes in specific rat uterine c...
9666068 - Expression of c-jun, hsp72 and gfap following repeated unilateral common carotid artery...
8162888 - Uv-responsive element (tgacaaca) from rat fibroblasts to human melanomas.
9731508 - Regulation of expression of the dna repair gene o6-methylguanine-dna methyltransferase ...
1372678 - Regulatory mutants and transcriptional control of the serratia marcescens extracellular...
8537398 - Efficient association of an amino-terminally extended form of human latent transforming...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-25
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  107     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-22     Completed Date:  2010-04-22     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4902-7     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cell Line
DNA Damage*
DNA-Binding Proteins / metabolism*
Nuclear Proteins / metabolism*
Proteasome Endopeptidase Complex / metabolism
Protein Processing, Post-Translational*
Proteins / metabolism*
Proto-Oncogene Proteins c-jun / metabolism*
Signal Transduction*
Tumor Suppressor Proteins / metabolism*
Ubiquitin / metabolism
Grant Support
MC_U132670600//Medical Research Council
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Nuclear Proteins; 0/Proteins; 0/Proto-Oncogene Proteins c-jun; 0/Tumor Suppressor Proteins; 0/Ubiquitin; 0/ornithine decarboxylase antizyme; 0/tumor suppressor protein p73; EC Endopeptidase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Stimulated coherent anti-Stokes Raman spectroscopy (CARS) resonances originate from double-slit inte...
Next Document:  The mouse ortholog of NEIL3 is a functional DNA glycosylase in vitro and in vivo.