|ZFIN ID: ZDB-PUB-140513-455|
Protein Interaction Between p53 and Δ113p53 Is Required for the Anti-Apoptotic Function of Δ113p53
Ou, Z., Yin, L., Chang, C., Peng, J., Chen, J.
|Source:||Journal of genetics and genomics = Yi chuan xue bao 41(2): 53-62 (Journal)|
|Registered Authors:||Peng, Jinrong|
|Keywords:||Apoptosis, Protein interaction, Zebrafish, p53, Δ113p53|
|PubMed:||24576456 Full text @ J. Genet. Genomics|
Ou, Z., Yin, L., Chang, C., Peng, J., Chen, J. (2014) Protein Interaction Between p53 and Δ113p53 Is Required for the Anti-Apoptotic Function of Δ113p53. Journal of genetics and genomics = Yi chuan xue bao. 41(2):53-62.
ABSTRACTZebrafish Δ113p53, an N-terminal truncated p53 isoform, is a p53-target gene that antagonises p53-mediated apoptotic activity. Interestingly, Δ113p53 does not act on p53 in a dominant-negative manner, but rather interferes with the p53 function by differentially modulating p53-target gene expression to protect cells from apoptosis. Previous studies showed that over-expressed Δ113p53 and p53 proteins formed a complex. However, it is not known whether endogenous p53 and Δ113p53 proteins also interact with each other, and if this interaction is required for Δ113p53 to inhibit the apoptotic activity of full-length p53. In this study, we used two available zebrafish p53 antibodies to address these questions. One, Zfp53-N, only recognises full-length p53, whereas the other, Zfp53-A7C10, detects both full-length p53 and Δ113p53. Using Zfp53-N for immunoprecipitation and Zfp53-A7C10 for detection, we demonstrated that endogenous Δ113p53 and full-length p53 induced by a DNA-damaging drug formed a complex in vivo. Furthermore, of the six Δ113p53 mutants we generated with different point mutations in the oligomerisation domain, two failed to interact with p53 and lost the ability to modulate p53-target gene expression and inhibit p53-induced cell apoptosis. However, those Δ113p53 mutants that could interact with p53 retained the ability to antagonise the apoptotic activity of p53. Therefore, our data demonstrated that protein-protein interaction between Δ113p53 and p53 is essential for the anti-apoptotic function of Δ113p53. In addition, the two Δ113p53 mutants that failed to interact with p53 are also useful for the study of the mechanisms of other functions of Δ113p53.