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A Tumor-Associated Mutation of FYVE-CENT Prevents Its Interaction with Beclin 1 and Interferes with Cytokinesis
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Sagona, Antonia P., Nezis, I. P., Bache, Kristi G., Haglund, Kaisa, Bakken, Anne Cathrine, Skotheim, Rolf I. and Stenmark, H. (Harald) (2011) A Tumor-Associated Mutation of FYVE-CENT Prevents Its Interaction with Beclin 1 and Interferes with Cytokinesis. PLoS ONE, Vol. 6 (No. 3). e17086. doi:10.1371/journal.pone.0017086 ISSN 1932-6203.
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Official URL: http://dx.doi.org/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.
Item Type: | Journal Article | ||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Journal or Publication Title: | PLoS ONE | ||||
Publisher: | PLOS | ||||
ISSN: | 1932-6203 | ||||
Official Date: | 2011 | ||||
Dates: |
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Volume: | Vol. 6 | ||||
Number: | No. 3 | ||||
Page Range: | e17086 | ||||
DOI: | 10.1371/journal.pone.0017086 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published |
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