Publication:
Apoptin induces apoptosis by changing the equilibrium between the stability of TAp73 and DNp73 isoforms through ubiquitin ligase PIR2

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Issued Date

2012

Resource Type

Article

File Type

application/pdf

ISSN

13608185

DOI

10.1007/s10495-012-0720-7

Other identifier(s)

2-s2.0-84865152602

Rights Holder(s)

Scopus

Bibliographic Citation

Apoptosis. Vol 17, No.8 (2012), p.762-776

Suggested Citation

Taebunpakul P., Sayan B.S., Flinterman M., Klanrit P., Gäken J., Odell E.W., Melino G., Tavassoli M. Apoptin induces apoptosis by changing the equilibrium between the stability of TAp73 and DNp73 isoforms through ubiquitin ligase PIR2. Apoptosis. Vol 17, No.8 (2012), p.762-776. doi:10.1007/s10495-012-0720-7 Retrieved from: https://hdl.handle.net/20.500.14740/6997

Title

Apoptin induces apoptosis by changing the equilibrium between the stability of TAp73 and DNp73 isoforms through ubiquitin ligase PIR2

Author(s)

Taebunpakul P.
 Sayan B.S.
 Flinterman M.
 Klanrit P.
 Gäken J.
 Odell E.W.
 Melino G.
 Tavassoli M.

Abstract

Apoptin, a protein derived from the chicken anaemia virus, induces cell death in various cancer cells but shows little or no cytotoxicity in normal cells. The mechanism of apoptin-induced cell death is currently unknown but it appears to induce apoptosis independent of p53 status. Here we show that p73, a p53 family member, is important in apoptin-induced apoptosis. In p53 deficient and/or mutated cells, apoptin induced the expression of TAp73 leading to the induction of apoptosis. Knockdown of p73 using siRNA resulted in a significant reduction in apoptin-induced cytotoxicity. The p53 and p73 pro-apoptotic target PUMA plays an important role in apoptin-induced cell death as knockdown of PUMA significantly reduced cell sensitivity to apoptin. Importantly, apoptin expression resulted in a marked increase in TAp73 protein stability. Investigation into the mechanisms of TAp73 stability showed that apoptin induced the expression of the ring finger domain ubiquitin ligase PIR2 which is involved in the degradation of the anti-apoptotic DNp73 isoform. Collectively, our results suggest a novel mechanism of apoptin-induced apoptosis through increased TAp73 stability and induction of PIR2 resulting in the degradation of DNp73 and activation of pro-apoptotic targets such as PUMA causing cancer cell death. © Springer Science+Business Media, LLC 2012.

Subject(s)

Apoptin
 Protein p53
 Protein p73
 PUMA protein
 Small interfering RNA
 Ubiquitin protein ligase
 Ubiquitin protein ligase E3
 Ubiquitin protein ligase PIR2
 Unclassified drug
 Apoptosis
 Article
 Controlled study
 Cytotoxicity
 Gyrovirus
 Human
 Human cell
 Priority journal
 Protein expression
 Protein stability
 RING finger motif
 Apoptosis
 Apoptosis Regulatory Proteins
 Capsid Proteins
 Cell Line, Tumor
 DNA-Binding Proteins
 G2 Phase Cell Cycle Checkpoints
 Half-Life
 Humans
 Nuclear Proteins
 Poly(ADP-ribose) Polymerases
 Protein Isoforms
 Protein Processing, Post-Translational
 Protein Stability
 Proteolysis
 Proto-Oncogene Proteins
 Tumor Suppressor Protein p53
 Tumor Suppressor Proteins
 Ubiquitin-Protein Ligases
 Ubiquitination
 Chicken anemia virus

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URI

https://hdl.handle.net/20.500.14740/6997

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Scopus: Year 1983-2021

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