RRC ID 67691
Author Aoyama K, Yuki R, Horiike Y, Kubota S, Yamaguchi N, Morii M, Ishibashi K, Nakayama Y, Kuga T, Hashimoto Y, Tomonaga T, Yamaguchi N.
Title Formation of long and winding nuclear F-actin bundles by nuclear c-Abl tyrosine kinase.
Journal Exp Cell Res
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.
Volume 319(20)
Pages 3251-68
Published 2013-12-10
DOI 10.1016/j.yexcr.2013.09.003
PII S0014-4827(13)00385-6
PMID 24041959
MeSH Actins / antagonists & inhibitors Actins / biosynthesis* Actins / chemistry Animals Binding Sites COS Cells Cell Nucleus / enzymology* Cell Nucleus / metabolism Chlorocebus aethiops HeLa Cells Humans Mice NIH 3T3 Cells Phosphorylation Proto-Oncogene Proteins c-abl / deficiency Proto-Oncogene Proteins c-abl / metabolism* Tyrosine / metabolism
IF 3.383
DNA material pENTR4-H1 (RDB04395)