The Ral/exocyst effector complex counters c-Jun N-terminal kinase-dependent apoptosis in Drosophila melanogaster

Maria Balakireva, Carine Rossé, Johanna Langevin, Yu Chen Chien, Michel Gho, Geneviève Gonzy-Treboul, Stéphanie Voegeling-Lemaire, Sandra Aresta, Jean Antoine Lepesant, Yohanns Bellaiche, Michael White, Jacques Camonis

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Ral GTPase activity is a crucial cell-autonomous factor supporting tumor initiation and progression. To decipher pathways impacted by Ral, we have generated null and hypomorph alleles of the Drosophila melanogaster Ral gene. Ral null animals were not viable. Reduced Ral expression in cells of the sensory organ lineage had no effect on cell division but led to postmitotic cell-specific apoptosis. Genetic epistasis and immunofluorescence in differentiating sensory organs suggested that Ral activity suppresses c-Jun N-terminal kinase (JNK) activation and induces p38 mitogen-activated protein (MAP) kinase activation. HPK1/GCK-like kinase (HGK), a MAP kinase kinase kinase kinase that can drive JNK activation, was found as an exocyst-associated protein in vivo. The exocyst is a Ral effector, and the epistasis between mutants of Ral and of msn, the fly ortholog of HGK, suggest the functional relevance of an exocyst/HGK interaction. Genetic analysis also showed that the exocyst is required for the execution of Ral function in apoptosis. We conclude that in Drosophila Ral counters apoptotic programs to support cell fate determination by acting as a negative regulator of JNK activity and a positive activator of p38 MAP kinase. We propose that the exocyst complex is Ral executioner in the JNK pathway and that a cascade from Ral to the exocyst to HGK would be a molecular basis of Ral action on JNK.

Original languageEnglish (US)
Pages (from-to)8953-8963
Number of pages11
JournalMolecular and Cellular Biology
Volume26
Issue number23
DOIs
StatePublished - Dec 2006

Fingerprint

JNK Mitogen-Activated Protein Kinases
Drosophila melanogaster
Phosphotransferases
Apoptosis
p38 Mitogen-Activated Protein Kinases
Genetic Epistasis
MAP Kinase Kinase Kinases
GTP Phosphohydrolases
Diptera
Cell Division
Drosophila
Fluorescent Antibody Technique
Alleles
GCK-like kinase
Genes
Neoplasms
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Balakireva, M., Rossé, C., Langevin, J., Chien, Y. C., Gho, M., Gonzy-Treboul, G., ... Camonis, J. (2006). The Ral/exocyst effector complex counters c-Jun N-terminal kinase-dependent apoptosis in Drosophila melanogaster. Molecular and Cellular Biology, 26(23), 8953-8963. https://doi.org/10.1128/MCB.00506-06

The Ral/exocyst effector complex counters c-Jun N-terminal kinase-dependent apoptosis in Drosophila melanogaster. / Balakireva, Maria; Rossé, Carine; Langevin, Johanna; Chien, Yu Chen; Gho, Michel; Gonzy-Treboul, Geneviève; Voegeling-Lemaire, Stéphanie; Aresta, Sandra; Lepesant, Jean Antoine; Bellaiche, Yohanns; White, Michael; Camonis, Jacques.

In: Molecular and Cellular Biology, Vol. 26, No. 23, 12.2006, p. 8953-8963.

Research output: Contribution to journalArticle

Balakireva, M, Rossé, C, Langevin, J, Chien, YC, Gho, M, Gonzy-Treboul, G, Voegeling-Lemaire, S, Aresta, S, Lepesant, JA, Bellaiche, Y, White, M & Camonis, J 2006, 'The Ral/exocyst effector complex counters c-Jun N-terminal kinase-dependent apoptosis in Drosophila melanogaster', Molecular and Cellular Biology, vol. 26, no. 23, pp. 8953-8963. https://doi.org/10.1128/MCB.00506-06
Balakireva, Maria ; Rossé, Carine ; Langevin, Johanna ; Chien, Yu Chen ; Gho, Michel ; Gonzy-Treboul, Geneviève ; Voegeling-Lemaire, Stéphanie ; Aresta, Sandra ; Lepesant, Jean Antoine ; Bellaiche, Yohanns ; White, Michael ; Camonis, Jacques. / The Ral/exocyst effector complex counters c-Jun N-terminal kinase-dependent apoptosis in Drosophila melanogaster. In: Molecular and Cellular Biology. 2006 ; Vol. 26, No. 23. pp. 8953-8963.
@article{40507938560b4443b732961be3987235,
title = "The Ral/exocyst effector complex counters c-Jun N-terminal kinase-dependent apoptosis in Drosophila melanogaster",
abstract = "Ral GTPase activity is a crucial cell-autonomous factor supporting tumor initiation and progression. To decipher pathways impacted by Ral, we have generated null and hypomorph alleles of the Drosophila melanogaster Ral gene. Ral null animals were not viable. Reduced Ral expression in cells of the sensory organ lineage had no effect on cell division but led to postmitotic cell-specific apoptosis. Genetic epistasis and immunofluorescence in differentiating sensory organs suggested that Ral activity suppresses c-Jun N-terminal kinase (JNK) activation and induces p38 mitogen-activated protein (MAP) kinase activation. HPK1/GCK-like kinase (HGK), a MAP kinase kinase kinase kinase that can drive JNK activation, was found as an exocyst-associated protein in vivo. The exocyst is a Ral effector, and the epistasis between mutants of Ral and of msn, the fly ortholog of HGK, suggest the functional relevance of an exocyst/HGK interaction. Genetic analysis also showed that the exocyst is required for the execution of Ral function in apoptosis. We conclude that in Drosophila Ral counters apoptotic programs to support cell fate determination by acting as a negative regulator of JNK activity and a positive activator of p38 MAP kinase. We propose that the exocyst complex is Ral executioner in the JNK pathway and that a cascade from Ral to the exocyst to HGK would be a molecular basis of Ral action on JNK.",
author = "Maria Balakireva and Carine Ross{\'e} and Johanna Langevin and Chien, {Yu Chen} and Michel Gho and Genevi{\`e}ve Gonzy-Treboul and St{\'e}phanie Voegeling-Lemaire and Sandra Aresta and Lepesant, {Jean Antoine} and Yohanns Bellaiche and Michael White and Jacques Camonis",
year = "2006",
month = "12",
doi = "10.1128/MCB.00506-06",
language = "English (US)",
volume = "26",
pages = "8953--8963",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "23",

}

TY - JOUR

T1 - The Ral/exocyst effector complex counters c-Jun N-terminal kinase-dependent apoptosis in Drosophila melanogaster

AU - Balakireva, Maria

AU - Rossé, Carine

AU - Langevin, Johanna

AU - Chien, Yu Chen

AU - Gho, Michel

AU - Gonzy-Treboul, Geneviève

AU - Voegeling-Lemaire, Stéphanie

AU - Aresta, Sandra

AU - Lepesant, Jean Antoine

AU - Bellaiche, Yohanns

AU - White, Michael

AU - Camonis, Jacques

PY - 2006/12

Y1 - 2006/12

N2 - Ral GTPase activity is a crucial cell-autonomous factor supporting tumor initiation and progression. To decipher pathways impacted by Ral, we have generated null and hypomorph alleles of the Drosophila melanogaster Ral gene. Ral null animals were not viable. Reduced Ral expression in cells of the sensory organ lineage had no effect on cell division but led to postmitotic cell-specific apoptosis. Genetic epistasis and immunofluorescence in differentiating sensory organs suggested that Ral activity suppresses c-Jun N-terminal kinase (JNK) activation and induces p38 mitogen-activated protein (MAP) kinase activation. HPK1/GCK-like kinase (HGK), a MAP kinase kinase kinase kinase that can drive JNK activation, was found as an exocyst-associated protein in vivo. The exocyst is a Ral effector, and the epistasis between mutants of Ral and of msn, the fly ortholog of HGK, suggest the functional relevance of an exocyst/HGK interaction. Genetic analysis also showed that the exocyst is required for the execution of Ral function in apoptosis. We conclude that in Drosophila Ral counters apoptotic programs to support cell fate determination by acting as a negative regulator of JNK activity and a positive activator of p38 MAP kinase. We propose that the exocyst complex is Ral executioner in the JNK pathway and that a cascade from Ral to the exocyst to HGK would be a molecular basis of Ral action on JNK.

AB - Ral GTPase activity is a crucial cell-autonomous factor supporting tumor initiation and progression. To decipher pathways impacted by Ral, we have generated null and hypomorph alleles of the Drosophila melanogaster Ral gene. Ral null animals were not viable. Reduced Ral expression in cells of the sensory organ lineage had no effect on cell division but led to postmitotic cell-specific apoptosis. Genetic epistasis and immunofluorescence in differentiating sensory organs suggested that Ral activity suppresses c-Jun N-terminal kinase (JNK) activation and induces p38 mitogen-activated protein (MAP) kinase activation. HPK1/GCK-like kinase (HGK), a MAP kinase kinase kinase kinase that can drive JNK activation, was found as an exocyst-associated protein in vivo. The exocyst is a Ral effector, and the epistasis between mutants of Ral and of msn, the fly ortholog of HGK, suggest the functional relevance of an exocyst/HGK interaction. Genetic analysis also showed that the exocyst is required for the execution of Ral function in apoptosis. We conclude that in Drosophila Ral counters apoptotic programs to support cell fate determination by acting as a negative regulator of JNK activity and a positive activator of p38 MAP kinase. We propose that the exocyst complex is Ral executioner in the JNK pathway and that a cascade from Ral to the exocyst to HGK would be a molecular basis of Ral action on JNK.

UR - http://www.scopus.com/inward/record.url?scp=33845202483&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845202483&partnerID=8YFLogxK

U2 - 10.1128/MCB.00506-06

DO - 10.1128/MCB.00506-06

M3 - Article

C2 - 17000765

AN - SCOPUS:33845202483

VL - 26

SP - 8953

EP - 8963

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 23

ER -