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Sica V, Bravo-San Pedro JM, Chen G, et al. Inhibitor of growth protein 4 interacts with Beclin 1 and represses autophagy. Oncotarget. 2017;8(52):89527-89538doi: 10.18632/oncotarget.19033.
Sica, V., Bravo-San Pedro, J. M., Chen, G., Mariño, G., Lachkar, S., Izzo, V., Maiuri, M. C., Niso-Santano, M., & Kroemer, G. (2017). Inhibitor of growth protein 4 interacts with Beclin 1 and represses autophagy. Oncotarget, 8(52), 89527-89538. https://doi.org/10.18632/oncotarget.19033
Sica, Valentina, et al. "Inhibitor of growth protein 4 interacts with Beclin 1 and represses autophagy." Oncotarget vol. 8,52 (2017): 89527-89538. doi: https://doi.org/10.18632/oncotarget.19033
Sica V, Bravo-San Pedro JM, Chen G, Mariño G, Lachkar S, Izzo V, Maiuri MC, Niso-Santano M, Kroemer G. Inhibitor of growth protein 4 interacts with Beclin 1 and represses autophagy. Oncotarget. 2017 Jul 06;8(52):89527-89538. doi: 10.18632/oncotarget.19033. eCollection 2017 Oct 27. PMID: 29163768; PMCID: PMC5685689.
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Oncotarget. 2017 Jul 06;8(52):89527-89538. doi: 10.18632/oncotarget.19033. eCollection 2017 Oct 27.

Inhibitor of growth protein 4 interacts with Beclin 1 and represses autophagy.

Oncotarget

Valentina Sica, José Manuel Bravo-San Pedro, Guo Chen, Guillermo Mariño, Sylvie Lachkar, Valentina Izzo, Maria Chiara Maiuri, Mireia Niso-Santano, Guido Kroemer

Affiliations

  1. Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
  2. Equipe 11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.
  3. Institut National de la Santé et de la Recherche Médicale, Paris, France.
  4. Université Pierre et Marie Curie, Paris, France.
  5. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.
  6. Departamento de Biología Fundamental, Instituto de Investigación Sanitaria del Principado de Asturias, Universidad de Oviedo, Spain.
  7. Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Cáceres, Spain.
  8. Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura, C.P, Cáceres, Cáceres, Spain.
  9. Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
  10. Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.

PMID: 29163768 PMCID: PMC5685689 DOI: 10.18632/oncotarget.19033

Abstract

Beclin 1 (BECN1) is a multifunctional protein that activates the pro-autophagic class III phosphatidylinositol 3-kinase (PIK3C3, best known as VPS34), yet also interacts with multiple negative regulators. Here we report that BECN1 interacts with inhibitor of growth family member 4 (ING4), a tumor suppressor protein that is best known for its capacity to interact with the tumor suppressor protein p53 (TP53) and the acetyltransferase E1A binding protein p300 (EP300). Removal of TP53 or EP300 did not affect the BECN1/ING4 interaction, which however was lost upon culture of cells in autophagy-inducing, nutrient free conditions. Depletion of ING4 stimulated the enzymatic activity of PIK3C3, as visualized by means of a red fluorescent protein-tagged short peptide (FYVE) that specifically binds to phosphatidylinositol-3-phosphate (PI3P)-containing subcellular vesicles and enhanced autophagy, as indicated by an enhanced lipidation of microtubule-associated proteins 1A/1B light chain 3 beta (LC3B) and the redistribution of a green-fluorescent protein (GFP)-LC3B fusion protein to cytoplasmic puncta. The generation of GFP-LC3B puncta stimulated by ING4 depletion was reduced by simultaneous depletion, or pharmacological inhibition, of PIK3C3/VPS34. In conclusion, ING4 acts as a negative regulator of the lipid kinase activity of the BECN1 complex, and starvation-induced autophagy is accompanied by the dissociation of the ING4/BECN1 interaction.

Keywords: Autophagy; ING4; PIK3C3; TP53; cancer

Conflict of interest statement

CONFLICTS OF INTEREST There is no conflict of interest.

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