title: A tumor-associated mutation of FYVE-CENT prevents its interaction with Beclin 1 and interferes with cytokinesis.
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.
authors: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: Antonia P
authors: AP
authors: Sagona
authors: Ioannis P
authors: IP
authors: Nezis
authors: Kristi G
authors: KG
authors: Bache
authors: Kaisa
authors: K
authors: Haglund
authors: Anne Cathrine
authors: AC
authors: Bakken
authors: Rolf I
authors: RI
authors: Skotheim
authors: Harald
authors: H
authors: Stenmark
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D000071186:Beclin-1; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D048749:Cytokinesis / Q000235:genetics / Q000502:physiology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D011123:Polyploidy; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D020798:Two-Hybrid System Techniques
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D002352:Carrier Proteins; D008565:Membrane Proteins; C528699:ZFYVE26 protein, human