p53 Target DDA3 binds ASPP2 and inhibits its stimulation on p53-mediated BAX activation

The p53 tumor suppressor functions in maintaining the integrity of the genome. We have previously reported that DDA3 is an oncoprotein transcriptionally regulated by p53. To explore mechanisms underlying DDA3 action, we searched for its interacting proteins by yeast two-hybrid screening, and identif...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2008-11, Vol.376 (2), p.395-398
Main Authors: Sun, Wei-Tzu, Hsieh, Pei-Chen, Chiang, Ming-Lun, Wang, Mei-Chih, Wang, Fung-Fang
Format: Article
Language:English
Subjects:
53BP2
Animals
Apoptosis
Apoptosis Regulatory Proteins
ASPP2
BAX
bcl-2-Associated X Protein - genetics
Carrier Proteins - antagonists & inhibitors
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Line, Tumor
DDA3
Genes, Reporter
Humans
Luciferases - genetics
p53
Phosphoproteins - genetics
Phosphoproteins - metabolism
Promoter Regions, Genetic
Protein Interaction Domains and Motifs
Protein Interaction Mapping
Transcriptional Activation
Tumor Suppressor Protein p53 - metabolism
Two-Hybrid System Techniques
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Summary:The p53 tumor suppressor functions in maintaining the integrity of the genome. We have previously reported that DDA3 is an oncoprotein transcriptionally regulated by p53. To explore mechanisms underlying DDA3 action, we searched for its interacting proteins by yeast two-hybrid screening, and identified ASPP2, a p53 binding protein, as its binding partner. The DDA3/ASPP2 binding was confirmed in vitro by GST pull-down and in vivo by immunofluorescence assay, which indicated colocalization of DDA3 and ASPP2. Interacting domain of DDA3 was mapped to amino acids 118–241, whereas both the N- and C-terminal regions of ASPP2 were capable of binding to DDA3. DDA3 dose-dependently inhibited ASPP2 in stimulating the p53-mediated BAX promoter activation without interfering the binding of ASPP2 to p53. Together these results identify ASPP2 as a bona fide DDA3 interacting protein, and suggest that the ASPP2/DDA3 interaction may inhibit ASPP2 in stimulating the apoptotic signaling of p53.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.08.168