标题：PACSIN 2 represses cellular migration through direct association with cyclin D1 but not its alternate splice form cyclin D1b
作者：Meng, Hui; Tian, Lifeng; Zhou, Jie; Li, Zhiping; Jiao, Xuanmao; Li, Wayne W.; Plomann, Markus; Xu, Zhishun; Lisanti, Michael P.; Wan 更多 作者机构：[Meng, Hui; Tian, Lifeng; Zhou, Jie; Li, Zhiping; Jiao, Xuanmao; Li, Wayne W.; Pestell, Richard G.] Thomas Jefferson Univ, Dept Canc Biol, Philadelphi 更多
通讯作者地址：[Pestell, RG]Thomas Jefferson Univ, Dept Canc Biol, Philadelphia, PA 19107 USA.
关键词：PACSIN 2; cyclin D1; polymorphism; cellular migration; cell spreading;; cancer
摘要：Cyclin D1 overexpression is a common feature of many human malignancies. Genomic deletion analysis has demonstrated a key role for cyclin D1 in cellular proliferation, angiogenesis and cellular migration. To investigate the mechanisms contributing to cyclin D1 functions, we purified cyclin D1a-associated complexes by affinity chromatography and identified the PACSIN 2 (protein kinase C and casein kinase substrate in neurons 2) protein by mass spectrometry. The PACSIN 2, but not the related PACSIN 1 and 3, directly bound wild-type cyclin D1 (cyclin D1a) at the carboxyl terminus and failed to bind cyclin D1b, the alternative splicing variant of cyclin D1. PACSIN 2 knockdown induced cellular migration and reduced cell spreading in LNCaP cells expressing cyclin D1a. In cyclin D1(-/-) mouse embryonic fibroblasts (MEFs), cyclin D1a, but not cyclin D1b, reduced the cell spreading to a polarized morphology. siPACSIN 2 had no effect on cellular migration of cyclin D1(-/-) MEFs. Cyclin D1a restored the migratory ability of cyclin D1(-/-) MEFs, which was further enhanced by knocking down PACSIN 2 with siRNA. The cyclin D1-associated protein, PACSIN 2, regulates cell spreading and migration, which are dependent on cyclin D1 expression.