Protein Interaction Between p53 and Δ113p53 Is Required for the Anti-Apoptotic Function of Δ113p53

Zhao Ou; Le Yin; Changqing Chang; Jinrong Peng; Jun Chen

doi:10.1016/j.jgg.2014.01.001

Volume 41 Issue 2

Feb. 2014

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Article Navigation > Journal of Genetics and Genomics > 2014 > 41(2): 53-62

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Protein Interaction Between p53 and Δ113p53 Is Required for the Anti-Apoptotic Function of Δ113p53

doi: 10.1016/j.jgg.2014.01.001

Zhao Ou^{a, #},
Le Yin^{a, #},
Changqing Chang^{c, #},
Jinrong Peng^b,
Jun Chen^a

a
College of Life Sciences, Zhejiang University, Hangzhou 310058, China
b
College of Animal Sciences, Zhejiang University, Hangzhou 310058, China
c
College of Natural Resources and Environment, South China Agricultural University, Guangzhou 510650, China

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Corresponding author: E-mail address: pengjr@zju.edu.cn (Jinrong Peng); E-mail address: chenjun2009@zju.edu.cn (Jun Chen)
Received Date: 2013-07-30
Accepted Date: 2014-01-09
Rev Recd Date: 2014-01-09

Available Online: 2014-01-20

Publish Date: 2014-02-20

Abstract

Abstract

Zebrafish 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 complexin 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.
- p53,
- Δ113p53,
- Protein interaction,
- Apoptosis,
- Zebrafish

These authors contributed equally to this work.

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References(21)

References

[1]	Aoubala, M., Murray-Zmijewski, F., Khoury, M.P. et al. p53 directly transactivates Delta133p53alpha, regulating cell fate outcome in response to DNA damage Cell Death Differ., 18 (2011),pp. 248-258
[2]	Berghmans, S., Murphey, R.D., Wienholds, E. et al. tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors Proc. Natl. Acad. Sci. USA, 102 (2005),pp. 407-412
[3]	Bernard, H., Garmy-Susini, B., Ainaoui, N. et al. The p53 isoform, Delta133p53alpha, stimulates angiogenesis and tumour progression Oncogene, 32 (2013),pp. 2150-2160
[4]	Bourdon, J.C. p53 family isoforms Curr. Pharm. Biotechnol., 8 (2007),pp. 332-336
[5]	Bourdon, J.C., Fernandes, K., Murray-Zmijewski, F. et al. p53 isoforms can regulate p53 transcriptional activity Genes Dev., 19 (2005),pp. 2122-2137
[6]	Brooks, C.L., Gu, W. New insights into p53 activation Cell Res., 20 (2010),pp. 614-621
[7]	Chen, J., Ng, S.M., Chang, C. et al. Genes Dev., 23 (2009),pp. 278-290
[8]	Chen, J., Peng, J. p53 isoform Delta113p53 in zebrafish Zebrafish, 6 (2009),pp. 389-395
[9]	Chen, J., Ruan, H., Ng, S.M. et al. Loss of function of def selectively up-regulates {Delta}113p53 expression to arrest expansion growth of digestive organs in zebrafish Genes Dev., 19 (2005),pp. 2900-2911
[10]	Ebrahimi, M., Boldrup, L., Coates, P.J. et al. Expression of novel p53 isoforms in oral lichen planus Oral Oncol., 44 (2008),pp. 156-161
[11]	Fujita, K., Mondal, A.M., Horikawa, I. et al. p53 isoforms Delta133p53 and p53beta are endogenous regulators of replicative cellular senescence Nat. Cell Biol., 11 (2009),pp. 1135-1142
[12]	Guo, L., Chua, J., Vijayakumar, D. et al. Detection of the 113p53 protein isoform: a p53-induced protein that feeds back on the p53 pathway to modulate the p53 response in zebrafish Cell Cycle, 9 (2010),pp. 1998-2007
[13]	Helton, E.S., Chen, X. p53 modulation of the DNA damage response J. Cell Biochem., 100 (2007),pp. 883-896
[14]	Kawaguchi, T., Kato, S., Otsuka, K. et al. The relationship among p53 oligomer formation, structure and transcriptional activity using a comprehensive missense mutation library Oncogene, 24 (2005),pp. 6976-6981
[15]	Khoury, M.P., Bourdon, J.C. p53 isoforms: an intracellular microprocessor? Genes Cancer, 2 (2011),pp. 453-465
[16]	Levine, A.J., Finlay, C.A., Hinds, P.W. Cell, 116 (2004),pp. S67-S69
[17]	Levine, A.J., Oren, M. The first 30 years of p53: growing ever more complex Nat. Rev. Cancer, 9 (2009),pp. 749-758
[18]	Marcel, V., Olivier, M., Mollereau, B. et al. First International p53 Isoforms Meeting: ‘p53 isoforms through evolution: from identification to biological function' Cell Death Differ., 18 (2011),pp. 563-564
[19]	Marcel, V., Vijayakumar, V., Fernandez-Cuesta, L. et al. p53 regulates the transcription of its Delta133p53 isoform through specific response elements contained within the TP53 P2 internal promoter Oncogene, 29 (2010),pp. 2691-2700
[20]	Okorokov, A.L., Orlova, E.V. Structural biology of the p53 tumour suppressor Curr. Opin. Struct. Biol., 19 (2009),pp. 197-202
[21]	Tao, T., Shi, H., Guan, Y.H. et al. Def defines a conserved nucleolar pathway that leads p53 to proteasome-independent degradation Cell Res., 23 (2013),pp. 620-634