Cyclin D1 Inhibits Cell Proliferation through Binding to PCNA and Cdk2

Cyclin D1 is known as a promoting factor for cell growth. We previously showed, however, that the expression of cyclin D1 increases markedly in senescent human fibroblastsin vitro.Here we investigate whether the overexpression of cyclin D1 inhibits cell proliferation. Colony formation after transfec...

Full description

Saved in:
Bibliographic Details
Published in:Experimental cell research 1999-02, Vol.246 (2), p.338-347
Main Authors: Fukami-Kobayashi, Junya, Mitsui, Youji
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
CDC2-CDC28 Kinases
Cdk2
Cell Division - drug effects
Cell Division - physiology
Cell Line
Cellular Senescence
CHO Cells
Cricetinae
cyclin D1
Cyclin D1 - genetics
Cyclin D1 - pharmacology
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinases - genetics
Cyclin-Dependent Kinases - metabolism
DNA Replication
Gene Expression
HeLa Cells
Humans
Mice
PCNA
Proliferating Cell Nuclear Antigen - genetics
Proliferating Cell Nuclear Antigen - metabolism
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
S Phase
Transfection
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cyclin D1 is known as a promoting factor for cell growth. We previously showed, however, that the expression of cyclin D1 increases markedly in senescent human fibroblastsin vitro.Here we investigate whether the overexpression of cyclin D1 inhibits cell proliferation. Colony formation after transfection with the cyclin D1 expression vector was repressed in NIH-3T3, TIG-1, CHO-K1, and HeLa cells, compared with those with mock and cyclin E expression vectors. A transient transfection assay demonstrated that the overexpression of cyclin D1 inhibited DNA synthesis of TIG-1 cells. The complexes of cyclin D1 with PCNA and cdk2 increased remarkably in senescent cells, compared with young counterparts. Excessive glutathioneS-transferase (GST)–cyclin D1 inhibited DNA replication and repressed cdk2-dependent kinase activityin vitro.DNA synthesis of NIH-3T3 transfectants with PCNA or cdk2 expression vectors was not inhibited by the overexpression of cyclin D1. These results indicate that an excessive level of cyclin D1 represses cell proliferation by inhibiting DNA replication and cdk2 activity through the binding of cyclin D1 to PCNA and cdk2, as it does in senescent cells.
ISSN:0014-4827
1090-2422
DOI:10.1006/excr.1998.4306