A tumor-associated mutation of FYVE-CENT prevents its interaction with Beclin 1 and interferes with cytokinesis

PLoS One. 2011 Mar 24;6(3):e17086. doi: 10.1371/journal.pone.0017086.

Abstract

The tumor suppressor activity of Beclin 1 (BECN1), a subunit of class III phosphatidylinositol 3-kinase complex, has been attributed to its regulation of apoptosis and autophagy. Here, we identify FYVE-CENT (ZFYVE26), a phosphatidylinositol 3-phosphate binding protein important for cytokinesis, as a novel interacting protein of Beclin 1. A mutation in FYVE-CENT (R1945Q) associated with breast cancer abolished the interaction between FYVE-CENT and Beclin 1, and reduced the localization of these proteins at the intercellular bridge during cytokinesis. Breast cancer cells containing the FYVE-CENT R1945Q mutation displayed a significant increase in cytokinetic profiles and bi-multinuclear phenotype. Both Beclin 1 and FYVE-CENT were found to be downregulated in advanced breast cancers. These findings suggest a positive feedback loop for recruitment of FYVE-CENT and Beclin 1 to the intercellular bridge during cytokinesis, and reveal a novel potential tumor suppressor mechanism for Beclin 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Beclin-1
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cytokinesis / genetics
  • Cytokinesis / physiology*
  • Female
  • HeLa Cells
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Polyploidy
  • Protein Binding / genetics
  • Protein Binding / physiology
  • RNA Interference
  • Two-Hybrid System Techniques

Substances

  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Carrier Proteins
  • Membrane Proteins
  • ZFYVE26 protein, human