title: Formation of long and winding nuclear F-actin bundles by nuclear c-Abl tyrosine kinase.
abstract: The non-receptor-type tyrosine kinase c-Abl is involved in actin dynamics in the cytoplasm. Having three nuclear localization signals (NLSs) and one nuclear export signal, c-Abl shuttles between the nucleus and the cytoplasm. Although monomeric actin and filamentous actin (F-actin) are present in the nucleus, little is known about the relationship between c-Abl and nuclear actin dynamics. Here, we show that nuclear-localized c-Abl induces nuclear F-actin formation. Adriamycin-induced DNA damage together with leptomycin B treatment accumulates c-Abl into the nucleus and increases the levels of nuclear F-actin. Treatment of c-Abl-knockdown cells with Adriamycin and leptomycin B barely increases the nuclear F-actin levels. Expression of nuclear-targeted c-Abl (NLS-c-Abl) increases the levels of nuclear F-actin even without Adriamycin, and the increased levels of nuclear F-actin are not inhibited by inactivation of Abl kinase activity. Intriguingly, expression of NLS-c-Abl induces the formation of long and winding bundles of F-actin within the nucleus in a c-Abl kinase activity-dependent manner. Furthermore, NLS-c-AblΔC, which lacks the actin-binding domain but has the full tyrosine kinase activity, is incapable of forming nuclear F-actin and in particular long and winding nuclear F-actin bundles. These results suggest that nuclear c-Abl plays critical roles in actin dynamics within the nucleus.
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Aoyama
authors.forename: Ryuzaburo
authors.initials: R
authors.lastname: Yuki
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Horiike
authors.forename: Sho
authors.initials: S
authors.lastname: Kubota
authors.forename: Noritaka
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Mariko
authors.initials: M
authors.lastname: Morii
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kuga
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomonaga
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamaguchi
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002467:Cell Nucleus / Q000201:enzymology* / Q000378:metabolism; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D016315:Proto-Oncogene Proteins c-abl / Q000172:deficiency / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000199:Actins; D014443:Tyrosine; D016315:Proto-Oncogene Proteins c-abl
keywords: Actin dynamics; Actin-biding domain; F-actin; Nucleus; Tyrosine phosphorylation; c-Abl tyrosine kinase