Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation

Xiong, Y., Zhang, H., Beach, D. (August 1993) Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation. Genes Dev, 7 (8). pp. 1572-83. ISSN 0890-9369 (Print)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/8101826
DOI: 10.1101/gad.7.8.1572

Abstract

In normal human diploid fibroblasts, cyclins of the A, B, and D classes each associate with cyclin-dependent kinases (CDKs), proliferating cell nuclear antigen (PCNA), and p21, thereby forming multiple independent quaternary complexes. Upon transformation of diploid fibroblasts with the DNA tumor virus SV40, or its transforming tumor antigen (T), the cyclin D/p21/CDK/PCNA complexes are disrupted. In transformed cells, CDK4 totally dissociates from cyclin D, PCNA, and p21 and, instead, associates exclusively with a polypeptide of 16 kD (p16). Quaternary complexes containing cyclins A or B1 and p21/CDK/PCNA also undergo subunit rearrangement in transformed cells. Both PCNA and p21 are no longer associated with CDC2-cyclin B1 binary complexes. Cyclin A complexes no longer contain p21, and a new 19-kD polypeptide (p19) is found in association with cyclin A. The pattern of subunit rearrangement of cyclin-CDK complexes in SV40-transformed cells is also shared in those containing adeno- or papilloma viral oncoproteins. Rearrangement also occurs in p53-deficient cells derived from Li-Fraumeni patients that carry no known DNA tumor virus. These findings suggest a mechanism by which oncogenic proteins alter the cell cycle of transformed cells.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Animals CDC2-CDC28 Kinases Cell Cycle Cell Line, Transformed Cell Transformation, Viral Cercopithecus aethiops Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinases Cyclins/ chemistry/physiology Electrophoresis, Polyacrylamide Gel Fibroblasts Hela Cells Humans Li-Fraumeni Syndrome/enzymology Molecular Sequence Data Neoplasm Proteins/chemistry Nuclear Proteins/chemistry Oncogene Protein p21(ras)/chemistry/metabolism Oncogene Proteins/ chemistry/ physiology Proliferating Cell Nuclear Antigen Protein Conformation Protein Kinases/ chemistry/metabolism Protein-Serine-Threonine Kinases Proto-Oncogene Proteins Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Simian virus 40 Structure-Activity Relationship Transformation, Genetic Tumor Suppressor Protein p53/metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Cyclins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > cdc2
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
organism description > virus > SV40
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > tumor suppressor
CSHL Authors:
Communities: CSHL labs > Beach lab
Depositing User: Matt Covey
Date: August 1993
Date Deposited: 19 Apr 2016 15:49
Last Modified: 03 Nov 2017 20:38
Related URLs:
URI: http://repository.cshl.edu/id/eprint/32517

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