Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation

M-L Dichtel-Danjoy, D Ma, P Dourlen, G Chatelain, F Napoletano, M Robin, M Corbet, C Levet, H Hafsi, P Hainaut, H D Ryoo, J-C Bourdon, B Mollereau

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Irradiated or injured cells enter apoptosis, and in turn, promote proliferation of surrounding unaffected cells. In Drosophila, apoptotic cells have an active role in proliferation, where the caspase Dronc and p53 induce mitogen expression and growth in the surrounding tissues. The Drosophila p53 gene structure is conserved and encodes at least two protein isoforms: a full-length isoform (Dp53) and an N-terminally truncated isoform (DΔNp53). Historically, DΔNp53 was the first p53 isoform identified and was thought to be responsible for all p53 biological activities. It was shown that DΔNp53 induces apoptosis by inducing the expression of IAP antagonists, such as Reaper. Here we investigated the roles of Dp53 and DΔNp53 in apoptosis and apoptosis-induced proliferation. We found that both isoforms were capable of activating apoptosis, but that they each induced distinct IAP antagonists. Expression of DΔNp53 induced Wingless (Wg) expression and enhanced proliferation in both 'undead cells' and in 'genuine' apoptotic cells. In contrast to DΔNp53, Dp53 did not induce Wg expression in the absence of the endogenous p53 gene. Thus, we propose that DΔNp53 is the main isoform that regulates apoptosis-induced proliferation. Understanding the roles of Drosophila p53 isoforms in apoptosis and in apoptosis-induced proliferation may shed new light on the roles of p53 isoforms in humans, with important implications in cancer biology.
Original languageEnglish
Pages (from-to)108-116
Number of pages9
JournalCell Death and Differentiation
Volume20
Issue number1
Early online date17 Aug 2012
DOIs
Publication statusPublished - Jan 2013

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Drosophila
Protein Isoforms
Apoptosis
p53 Genes
Caspases
Mitogens
Growth
Neoplasms

Keywords

  • animals
  • tumor suppressor protein p53
  • apoptosis
  • animals, genetically modified
  • drosophila
  • cell growth processes
  • signal transduction
  • protein isoforms

Cite this

Dichtel-Danjoy, M-L., Ma, D., Dourlen, P., Chatelain, G., Napoletano, F., Robin, M., ... Mollereau, B. (2013). Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation. Cell Death and Differentiation, 20(1), 108-116. https://doi.org/10.1038/cdd.2012.100
Dichtel-Danjoy, M-L ; Ma, D ; Dourlen, P ; Chatelain, G ; Napoletano, F ; Robin, M ; Corbet, M ; Levet, C ; Hafsi, H ; Hainaut, P ; Ryoo, H D ; Bourdon, J-C ; Mollereau, B. / Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation. In: Cell Death and Differentiation. 2013 ; Vol. 20, No. 1. pp. 108-116.
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Dichtel-Danjoy, M-L, Ma, D, Dourlen, P, Chatelain, G, Napoletano, F, Robin, M, Corbet, M, Levet, C, Hafsi, H, Hainaut, P, Ryoo, HD, Bourdon, J-C & Mollereau, B 2013, 'Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation', Cell Death and Differentiation, vol. 20, no. 1, pp. 108-116. https://doi.org/10.1038/cdd.2012.100

Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation. / Dichtel-Danjoy, M-L; Ma, D; Dourlen, P; Chatelain, G; Napoletano, F; Robin, M; Corbet, M; Levet, C; Hafsi, H; Hainaut, P; Ryoo, H D; Bourdon, J-C; Mollereau, B.

In: Cell Death and Differentiation, Vol. 20, No. 1, 01.2013, p. 108-116.

Research output: Contribution to journalArticle

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T1 - Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation

AU - Dichtel-Danjoy, M-L

AU - Ma, D

AU - Dourlen, P

AU - Chatelain, G

AU - Napoletano, F

AU - Robin, M

AU - Corbet, M

AU - Levet, C

AU - Hafsi, H

AU - Hainaut, P

AU - Ryoo, H D

AU - Bourdon, J-C

AU - Mollereau, B

PY - 2013/1

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N2 - Irradiated or injured cells enter apoptosis, and in turn, promote proliferation of surrounding unaffected cells. In Drosophila, apoptotic cells have an active role in proliferation, where the caspase Dronc and p53 induce mitogen expression and growth in the surrounding tissues. The Drosophila p53 gene structure is conserved and encodes at least two protein isoforms: a full-length isoform (Dp53) and an N-terminally truncated isoform (DΔNp53). Historically, DΔNp53 was the first p53 isoform identified and was thought to be responsible for all p53 biological activities. It was shown that DΔNp53 induces apoptosis by inducing the expression of IAP antagonists, such as Reaper. Here we investigated the roles of Dp53 and DΔNp53 in apoptosis and apoptosis-induced proliferation. We found that both isoforms were capable of activating apoptosis, but that they each induced distinct IAP antagonists. Expression of DΔNp53 induced Wingless (Wg) expression and enhanced proliferation in both 'undead cells' and in 'genuine' apoptotic cells. In contrast to DΔNp53, Dp53 did not induce Wg expression in the absence of the endogenous p53 gene. Thus, we propose that DΔNp53 is the main isoform that regulates apoptosis-induced proliferation. Understanding the roles of Drosophila p53 isoforms in apoptosis and in apoptosis-induced proliferation may shed new light on the roles of p53 isoforms in humans, with important implications in cancer biology.

AB - Irradiated or injured cells enter apoptosis, and in turn, promote proliferation of surrounding unaffected cells. In Drosophila, apoptotic cells have an active role in proliferation, where the caspase Dronc and p53 induce mitogen expression and growth in the surrounding tissues. The Drosophila p53 gene structure is conserved and encodes at least two protein isoforms: a full-length isoform (Dp53) and an N-terminally truncated isoform (DΔNp53). Historically, DΔNp53 was the first p53 isoform identified and was thought to be responsible for all p53 biological activities. It was shown that DΔNp53 induces apoptosis by inducing the expression of IAP antagonists, such as Reaper. Here we investigated the roles of Dp53 and DΔNp53 in apoptosis and apoptosis-induced proliferation. We found that both isoforms were capable of activating apoptosis, but that they each induced distinct IAP antagonists. Expression of DΔNp53 induced Wingless (Wg) expression and enhanced proliferation in both 'undead cells' and in 'genuine' apoptotic cells. In contrast to DΔNp53, Dp53 did not induce Wg expression in the absence of the endogenous p53 gene. Thus, we propose that DΔNp53 is the main isoform that regulates apoptosis-induced proliferation. Understanding the roles of Drosophila p53 isoforms in apoptosis and in apoptosis-induced proliferation may shed new light on the roles of p53 isoforms in humans, with important implications in cancer biology.

KW - animals

KW - tumor suppressor protein p53

KW - apoptosis

KW - animals, genetically modified

KW - drosophila

KW - cell growth processes

KW - signal transduction

KW - protein isoforms

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SN - 1350-9047

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Dichtel-Danjoy M-L, Ma D, Dourlen P, Chatelain G, Napoletano F, Robin M et al. Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation. Cell Death and Differentiation. 2013 Jan;20(1):108-116. https://doi.org/10.1038/cdd.2012.100