title: Nuclear F-actin enhances the transcriptional activity of β-catenin by increasing its nuclear localization and binding to chromatin.
abstract: Actin plays multiple roles both in the cytoplasm and in the nucleus. Cytoplasmic actin, in addition to its structural role in the cytoskeleton, also contributes to the subcellular localization of transcription factors by interacting with them or their partners. The transcriptional cofactor β-catenin, which acts as an intracellular transducer of canonical Wnt signaling, indirectly associates with the cytoplasmic filamentous actin (F-actin). Recently, it has been observed that F-actin is transiently formed within the nucleus in response to serum stimulation and integrin signaling, and also during gene reprogramming. Despite these earlier observations, information about the function of nuclear F-actin is poorly defined. Here, by facilitating the accumulation of nuclear actin artificially, we demonstrate that polymerizing nuclear actin enhanced the nuclear accumulation and transcriptional function of β-catenin. Our results also show that the nuclear F-actin colocalizes with β-catenin and enhances the binding of β-catenin to the downstream target genes of the Wnt/β-catenin signaling pathway, including the genes for the cell cycle regulators c-myc and cyclin D, and the OCT4 gene. Nuclear F-actin itself also associated with these genes. Since Wnt/β-catenin signaling has important roles in cell differentiation and pluripotency, our observations suggest that nuclear F-actin formed during these biological processes is involved in regulating Wnt/β-catenin signaling.
authors.affiliation: Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Tsutsumidori-Amamiyamachi 1-1, Aoba-ku, Sendai, 981-8555, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Yamazaki
authors.affiliation: Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Tsutsumidori-Amamiyamachi 1-1, Aoba-ku, Sendai, 981-8555, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Physiology and Biophysics, University of Illinois at Chicago, 835 South Wolcott Avenue, Chicago, IL, 60612, USA.
authors.forename: Primal
authors.initials: P
authors.lastname: de Lanerolle
authors.affiliation: Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Tsutsumidori-Amamiyamachi 1-1, Aoba-ku, Sendai, 981-8555, Japan. mharata@biochem.tohoku.ac.jp.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Harata
mesh_terms: D000199:Actins / Q000378:metabolism*; D001665:Binding Sites; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation; D051176:beta Catenin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000199:Actins; C495270:CTNNB1 protein, human; D002843:Chromatin; D051176:beta Catenin
keywords: Chromatin binding; Nuclear actin; Transcription; Wnt signaling; β-Catenin