title: NAC1 is an actin-binding protein that is essential for effective cytokinesis in cancer cells.
abstract: 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.
authors: Department of Pathology, Pathobiology Graduate Program, Oncology Center, Johns Hopkins University, Baltimore, Maryland 21231, USA.
authors: Kai Lee
authors: KL
authors: Yap
authors: Stephanie I
authors: SI
authors: Fraley
authors: Michelle M
authors: MM
authors: Thiaville
authors: Natini
authors: N
authors: Jinawath
authors: Kentaro
authors: K
authors: Nakayama
authors: Jianlong
authors: J
authors: Wang
authors: Tian-Li
authors: TL
authors: Wang
authors: Denis
authors: D
authors: Wirtz
authors: Ie-Ming
authors: IeM
authors: Shih
mesh_terms: D000199:Actins / Q000378:metabolism*; D048749:Cytokinesis / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D051304:Profilins / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism*
chemical_list: D000199:Actins; C516477:NACC1 protein, human; D009363:Neoplasm Proteins; C495738:PFN1 protein, human; D051304:Profilins; D012097:Repressor Proteins