期刊
CELL CYCLE
卷 10, 期 1, 页码 73-81出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.10.1.14243
关键词
PACSIN 2; cyclin D1; polymorphism; cellular migration; cell spreading; cancer
类别
资金
- Susan Komen Breast Cancer Foundation [BCTR0504227]
- National Institutes of Health [R01CA70896, R01CA75503, R01CA86072]
- NIH Cancer Center [P30CA56036]
- China Scholarship Council
- Pennsylvania Department of Health
- NATIONAL CANCER INSTITUTE [R01CA086072, R01CA075503, P30CA056036, R01CA070896] Funding Source: NIH RePORTER
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.
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