NAC1 Is an Actin-Binding Protein That Is Essential for Effective Cytokinesis in Cancer Cells
| Autor: | Tian Li Wang, Michelle M. Thiaville, Denis Wirtz, Ie Ming Shih, Natini Jinawath, Kai Lee Yap, Stephanie I. Fraley, Kentaro Nakayama, Jian-Long Wang |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Arp2/3 complex macromolecular substances Septin Article Profilins Neoplasms Humans Actin-binding protein Actin Cytokinesis biology Actin monomer binding Actins Neoplasm Proteins Cell biology Repressor Proteins HEK293 Cells Phenotype Oncology Profilin Cancer cell MCF-7 Cells biology.protein HeLa Cells |
| Zdroj: | Cancer Research. 72:4085-4096 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-12-0302 |
| Popis: | NAC1 is a transcriptional corepressor protein that is essential to sustain cancer cell proliferation and migration. However, the underlying molecular mechanisms of NAC1 function in cancer cells remain unknown. In this study, we show that NAC1 functions as an actin monomer–binding protein. The conserved BTB protein interaction domain in NAC1 is the minimal region for actin binding. Disrupting NAC1 complex function by dominant-negative or siRNA strategies reduced cell retraction and abscission during late-stage cytokinesis, causing multinucleation in cancer cells. In Nac1-deficient murine fibroblasts, restoring NAC1 expression was sufficient to partially avert multinucleation. We found that siRNA-mediated silencing of the actin-binding protein profilin-1 in cancer cells caused a similar multinucleation phenotype and that NAC1 modulated the binding of actin to profillin-1. Taken together, our results indicate that the NAC1/actin/profilin-1 complex is crucial for cancer cell cytokinesis, with a variety of important biologic and clinical implications. Cancer Res; 72(16); 4085–96. ©2012 AACR. |
| Databáze: | OpenAIRE |
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