Genetic models of apoptosis-induced proliferation decipher activation of JNK and identify a requirement of EGFR signaling for tissue regenerative responses in Drosophila

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Genetic models of apoptosis-induced proliferation decipher activation of JNK and identify a requirement of EGFR signaling for tissue regenerative responses in Drosophila. / Fan, Yun; Wang, Shiuan; Hernandez, Jacob; Yenigun, Vildan Betul; Hertlein, Gillian; Fogarty, Caitlin E; Lindblad, Jillian L; Bergmann, Andreas.

In: PLoS Genetics, Vol. 10, No. 1, e1004131, 30.01.2014.

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Fan, Yun ; Wang, Shiuan ; Hernandez, Jacob ; Yenigun, Vildan Betul ; Hertlein, Gillian ; Fogarty, Caitlin E ; Lindblad, Jillian L ; Bergmann, Andreas. / Genetic models of apoptosis-induced proliferation decipher activation of JNK and identify a requirement of EGFR signaling for tissue regenerative responses in Drosophila. In: PLoS Genetics. 2014 ; Vol. 10, No. 1.

Bibtex

@article{90b7cc1cae77477482127a9d1d633c39,
title = "Genetic models of apoptosis-induced proliferation decipher activation of JNK and identify a requirement of EGFR signaling for tissue regenerative responses in Drosophila",
abstract = "Recent work in several model organisms has revealed that apoptotic cells are able to stimulate neighboring surviving cells to undergo additional proliferation, a phenomenon termed apoptosis-induced proliferation. This process depends critically on apoptotic caspases such as Dronc, the Caspase-9 ortholog in Drosophila, and may have important implications for tumorigenesis. While it is known that Dronc can induce the activity of Jun N-terminal kinase (JNK) for apoptosis-induced proliferation, the mechanistic details of this activation are largely unknown. It is also controversial if JNK activity occurs in dying or in surviving cells. Signaling molecules of the Wnt and BMP families have been implicated in apoptosis-induced proliferation, but it is unclear if they are the only ones. To address these questions, we have developed an efficient assay for screening and identification of genes that regulate or mediate apoptosis-induced proliferation. We have identified a subset of genes acting upstream of JNK activity including Rho1. We also demonstrate that JNK activation occurs both in apoptotic cells as well as in neighboring surviving cells. In a genetic screen, we identified signaling by the EGFR pathway as important for apoptosis-induced proliferation acting downstream of JNK signaling. These data underscore the importance of genetic screening and promise an improved understanding of the mechanisms of apoptosis-induced proliferation.",
keywords = "Animals, Apoptosis, Carcinogenesis, Caspases, Cell Proliferation, Drosophila Proteins, Drosophila melanogaster, Humans, MAP Kinase Kinase 4, Models, Genetic, Neoplasms, Receptor, Epidermal Growth Factor, Receptors, Invertebrate Peptide, Regeneration, Wnt Signaling Pathway, rho GTP-Binding Proteins",
author = "Yun Fan and Shiuan Wang and Jacob Hernandez and Yenigun, {Vildan Betul} and Gillian Hertlein and Fogarty, {Caitlin E} and Lindblad, {Jillian L} and Andreas Bergmann",
year = "2014",
month = jan,
day = "30",
doi = "10.1371/journal.pgen.1004131",
language = "English",
volume = "10",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science (PLOS)",
number = "1",

}

RIS

TY - JOUR

T1 - Genetic models of apoptosis-induced proliferation decipher activation of JNK and identify a requirement of EGFR signaling for tissue regenerative responses in Drosophila

AU - Fan, Yun

AU - Wang, Shiuan

AU - Hernandez, Jacob

AU - Yenigun, Vildan Betul

AU - Hertlein, Gillian

AU - Fogarty, Caitlin E

AU - Lindblad, Jillian L

AU - Bergmann, Andreas

PY - 2014/1/30

Y1 - 2014/1/30

N2 - Recent work in several model organisms has revealed that apoptotic cells are able to stimulate neighboring surviving cells to undergo additional proliferation, a phenomenon termed apoptosis-induced proliferation. This process depends critically on apoptotic caspases such as Dronc, the Caspase-9 ortholog in Drosophila, and may have important implications for tumorigenesis. While it is known that Dronc can induce the activity of Jun N-terminal kinase (JNK) for apoptosis-induced proliferation, the mechanistic details of this activation are largely unknown. It is also controversial if JNK activity occurs in dying or in surviving cells. Signaling molecules of the Wnt and BMP families have been implicated in apoptosis-induced proliferation, but it is unclear if they are the only ones. To address these questions, we have developed an efficient assay for screening and identification of genes that regulate or mediate apoptosis-induced proliferation. We have identified a subset of genes acting upstream of JNK activity including Rho1. We also demonstrate that JNK activation occurs both in apoptotic cells as well as in neighboring surviving cells. In a genetic screen, we identified signaling by the EGFR pathway as important for apoptosis-induced proliferation acting downstream of JNK signaling. These data underscore the importance of genetic screening and promise an improved understanding of the mechanisms of apoptosis-induced proliferation.

AB - Recent work in several model organisms has revealed that apoptotic cells are able to stimulate neighboring surviving cells to undergo additional proliferation, a phenomenon termed apoptosis-induced proliferation. This process depends critically on apoptotic caspases such as Dronc, the Caspase-9 ortholog in Drosophila, and may have important implications for tumorigenesis. While it is known that Dronc can induce the activity of Jun N-terminal kinase (JNK) for apoptosis-induced proliferation, the mechanistic details of this activation are largely unknown. It is also controversial if JNK activity occurs in dying or in surviving cells. Signaling molecules of the Wnt and BMP families have been implicated in apoptosis-induced proliferation, but it is unclear if they are the only ones. To address these questions, we have developed an efficient assay for screening and identification of genes that regulate or mediate apoptosis-induced proliferation. We have identified a subset of genes acting upstream of JNK activity including Rho1. We also demonstrate that JNK activation occurs both in apoptotic cells as well as in neighboring surviving cells. In a genetic screen, we identified signaling by the EGFR pathway as important for apoptosis-induced proliferation acting downstream of JNK signaling. These data underscore the importance of genetic screening and promise an improved understanding of the mechanisms of apoptosis-induced proliferation.

KW - Animals

KW - Apoptosis

KW - Carcinogenesis

KW - Caspases

KW - Cell Proliferation

KW - Drosophila Proteins

KW - Drosophila melanogaster

KW - Humans

KW - MAP Kinase Kinase 4

KW - Models, Genetic

KW - Neoplasms

KW - Receptor, Epidermal Growth Factor

KW - Receptors, Invertebrate Peptide

KW - Regeneration

KW - Wnt Signaling Pathway

KW - rho GTP-Binding Proteins

U2 - 10.1371/journal.pgen.1004131

DO - 10.1371/journal.pgen.1004131

M3 - Article

C2 - 24497843

VL - 10

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 1

M1 - e1004131

ER -