Document Actions
Senescent cells fail to express cdc2, cy ... response to mitogen stimulation
Senescent cells fail to express cdc2, cycA, and cycB in response to mitogen stimulation.
39
Senescent human diploid fibroblasts (HDF) contain no detectable cdc2 mRNA or p34cdc2 protein. Similarly, young quiescent HDF have only low levels of cdc2 mRNA and protein. After serum stimulation, quiescent HDF accumulate increasing amounts of cdc2 mRNA and protein and go through DNA synthesis and mitosis. In contrast, serum-stimulated senescent HDF fail to accumulate detectable amounts of cdc2 mRNA and protein and fail to enter S phase. Mitosis is likewise deficient in senescent cells even when they have been induced to synthesize DNA by simian virus 40 large tumor antigen. Since p34cdc2 or its homologues appear to be required for DNA synthesis and mitosis in eukaryotes, a lack of these molecules in serum-stimulated senescent HDF could be an important reason for their inability to enter S phase or mitosis. Nuclear microinjection of cdc2 DNA into senescent HDF causes rounding up of the cells but no induction of DNA synthesis. Since cyclins A and B are important cofactors of the protein kinase activity of p34cdc2 or its homologues, we analyzed expression of these genes in serum-stimulated senescent HDF and determined that they contain little or no cycA or cycB mRNA. These deficiencies may be relevant to the lack of DNA synthesis and mitosis in senescent HDF.
Stein GH, Drullinger LF, Robetorye RS, Pereira-Smith OM, Smith JR
Proceedings of the National Academy of Sciences of the United States of America
1991-12-15 00:00
88
24
11012-6
Amino Acid Sequence,Blotting, Northern,CDC2 Protein Kinase,Cell Aging,Cell Line,Cell Nucleus,DNA Probes,DNA Replication,Fibroblasts,Gene Expression,Humans,Immunoblotting,Mitogens,Mitosis,Molecular Sequence Data,Poly A,RNA,RNA, Messenger,Transcription, Genetic,Transfection,DNA Probes,Mitogens,RNA, Messenger,Poly A,RNA,CDC2 Protein Kinase
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309-0347
Proc. Natl. Acad. Sci. U.S.A.
NIA AG00947, NIA AG05333, NIA T32-AG00183
0027-8424
1098
True
1722313
