p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase

Zhang, H., Kobayashi, R., Galaktionov, K., Beach, D. (September 1995) p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase. Cell, 82 (6). pp. 915-25. ISSN 0092-8674 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/7553852
DOI: 10.1016/0092-8674(95)90271-6

Abstract

In normal human fibroblasts, cyclin A-CDK2 exists in a quaternary complex that contains p21 and PCNA. In many transformed cells, p21 disappears, and a substantial fraction of cyclin A-CDK2 complexes with p9CKS1/CKS2, p19, and p45. To investigate the significance of these rearrangements, we have isolated cDNAs encoding p19 and p45. In vitro reconstitution demonstrated that binding of p19 to cyclin A-CDK2 requires p45. Addition of these proteins to the kinase had no substantial effect on the kinase activity in vitro. Interference with p45 function in vivo by microinjection of antibodies or antisense oligonucleotides prevented entry into S phase in both normal and transformed cells. Cyclin A-CDK2 has previously been identified as a kinase whose activity is essential for S phase. Our results identify p45 as an essential element of this activity. The abundance of p45 is greatly increased in many transformed cells. This could result in changes in cell cycle control that contribute to the process of cellular transformation.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Base Sequence CDC2-CDC28 Kinases Cell Cycle/physiology Cell Cycle Proteins/ physiology Comparative Study Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinases/metabolism/ ultrastructure Cyclins/metabolism/ ultrastructure DNA, Complementary/isolation & purification Fibroblasts/cytology Hela Cells Humans Kidney/cytology Molecular Sequence Data Molecular Weight Protein Binding/physiology Protein-Serine-Threonine Kinases/metabolism/ ultrastructure Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. S Phase/ physiology S-Phase Kinase-Associated Proteins Transformation, Genetic/physiology
Subjects: bioinformatics > genomics and proteomics > design > amino acid design
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > cDNA
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts

organism description > animal > mammal > primates > hominids > human
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
CSHL Authors:
Communities: CSHL labs > Beach lab
CSHL labs > Kobayashi lab
Depositing User: Jessica Koos
Date: 22 September 1995
Date Deposited: 31 Jul 2014 15:27
Last Modified: 31 Jul 2014 15:27
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30656

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