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iLABMED 2023, 1(2): 121-131 https://doi.org/10.1002/ila2.21
Original Article | Open Access | Issue | Published: 11 July 2023

An iASPP‐derived short peptide restores p53‐mediated cell death in cancers with wild‐type p53

Show Author's Information Shi Qiu1,,  Wei Qi2,,  Wen Wu3,  Qian Qiu4,  Jiali Ma1,  Yingjun Li1,  Wenhui Fan1,  Junli Li5,  Yang Xu2( ),  Hai Chen6( ),  Jie Liu1( )
Clinical Laboratory, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, China
Department of Oncology, Beidaihe Rehabilitation Center of PLA, Qinhuangdao, Hebei, China
Department of Ultrasound, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, China
Post‐Doctoral Research Center, Chongqing Public Health Medical Center, Chongqing, China
Department of Chinese Medicine, Liulitun Community Services Center, Beijing, China
Department of General Surgery, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, China

Shi Qiu and Wei Qi contributed equally to this work.

Keywords:
apoptosis, p53, iASPP protein, short peptide
Cite this article:
Qiu S, Qi W, Wu W, et al. An iASPP‐derived short peptide restores p53‐mediated cell death in cancers with wild‐type p53. iLABMED, 2023, 1(2): 121-131. https://doi.org/10.1002/ila2.21
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Abstract Full text About this article
Background

Inhibitor of apoptosis‐stimulating protein of p53 (iASPP) is an evolutionarily conserved p53 inhibitor. Mechanistically, iASPP can accelerate tumorigenesis by inhibiting the transactivation function of p53. Targeting the interaction between iASPP and p53 may be a potential therapy for restoring the activity of p53 in tumors.

Methods

We constructed an iASPP‐derived peptide, called A8, that was derived from the C‐terminus of iASPP. Here, we transfected A8 into two wild‐type (WT) p53 cell lines, U2OS and A549, and then determined the number of apoptotic cells. The mechanism by which A8 affected apoptosis was further examined by immunoprecipitation (IP), Dual‐Luciferase reporter assays, and chromatin IP assays. Real‐time polymerase chain reaction and western blots were also used to examine the expression levels of apoptosis‐related factors.

Results

Our data demonstrate that A8 can increase apoptosis rates in WT p53 cell lines. Functional analysis suggested that A8 restored the transcriptional function and DNA binding activities of p53 toward the Bax and PUMA gene promoters. Moreover, A8 reduced cell proliferation and inhibited tumor growth in xenograft nude mice.

Conclusions

These data provide a new approach for restoring the tumor suppressor function of p53 in cancer cells that express WT p53 and therefore may serve as a novel cancer treatment strategy.


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Abstract
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About this article

An iASPP‐derived short peptide restores p53‐mediated cell death in cancers with wild‐type p53

Show Author's information Shi Qiu1,, Wei Qi2,, Wen Wu3, Qian Qiu4, Jiali Ma1, Yingjun Li1, Wenhui Fan1, Junli Li5, Yang Xu2( ), Hai Chen6( ), Jie Liu1( )
Clinical Laboratory, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, China
Department of Oncology, Beidaihe Rehabilitation Center of PLA, Qinhuangdao, Hebei, China
Department of Ultrasound, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, China
Post‐Doctoral Research Center, Chongqing Public Health Medical Center, Chongqing, China
Department of Chinese Medicine, Liulitun Community Services Center, Beijing, China
Department of General Surgery, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, China

Shi Qiu and Wei Qi contributed equally to this work.

Abstract

Background

Inhibitor of apoptosis‐stimulating protein of p53 (iASPP) is an evolutionarily conserved p53 inhibitor. Mechanistically, iASPP can accelerate tumorigenesis by inhibiting the transactivation function of p53. Targeting the interaction between iASPP and p53 may be a potential therapy for restoring the activity of p53 in tumors.

Methods

We constructed an iASPP‐derived peptide, called A8, that was derived from the C‐terminus of iASPP. Here, we transfected A8 into two wild‐type (WT) p53 cell lines, U2OS and A549, and then determined the number of apoptotic cells. The mechanism by which A8 affected apoptosis was further examined by immunoprecipitation (IP), Dual‐Luciferase reporter assays, and chromatin IP assays. Real‐time polymerase chain reaction and western blots were also used to examine the expression levels of apoptosis‐related factors.

Results

Our data demonstrate that A8 can increase apoptosis rates in WT p53 cell lines. Functional analysis suggested that A8 restored the transcriptional function and DNA binding activities of p53 toward the Bax and PUMA gene promoters. Moreover, A8 reduced cell proliferation and inhibited tumor growth in xenograft nude mice.

Conclusions

These data provide a new approach for restoring the tumor suppressor function of p53 in cancer cells that express WT p53 and therefore may serve as a novel cancer treatment strategy.

Keywords: apoptosis, p53, iASPP protein, short peptide

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Publication history

Received: 03 April 2023
Accepted: 14 May 2023
Published: 11 July 2023
Issue date: September 2023

Copyright

© 2023 The Authors. Tsinghua University Press.

Acknowledgements

ACKNOWLEDGMENTS

We are grateful to Takara Biotechnology (Dalian) Co., Ltd., Gene Chem Co., Ltd., and Kangchen Bio‐tech Inc. for technical assistance. We also thank members of the laboratory for assistance.

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This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

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