Relative mitogenic activities of wild-type and retinoblastoma binding-defective SV40 T antigens in serum-deprived and senescent human diploid fibroblasts.
A novel gene transfer approach was used to investigate whether the retinoblastoma (Rb)-binding domain of simian virus 40 (SV40) T antigen is required for efficient T antigen-mediated stimulation of DNA synthesis is quiescent or senescent human embryo fibroblasts. In senescent cells, comparison between wild-type T antigen and a mutant defective in Rb binding (Glu-107-->Lys) revealed the latter to have approximately 15-fold lower activity. In contrast, comparison of wild-type and Rb- T antigens in serum-deprived quiescent cells revealed a much smaller (1.8-fold) difference. Surprisingly, an 18-fold differential could be induced by treating quiescent cells with the differentiating agent sodium butyrate. These results suggest that the role of Rb in control of the cell cycle is strongly dependent on the physiological state of the cell and the mechanism of growth arrest.
Sakamoto
K
K
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Howard
T
T
Ogryzko
V
V
Xu
N Z
NZ
Corsico
C C
CC
Jones
D H
DH
Howard
B
B
D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002453:Cell Cycle; D002455:Cell Division; D016922:Cellular Senescence; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts; D006801:Humans; D008934:Mitogens / Q000502:physiology*; D009154:Mutation; D015375:Receptors, Interleukin-2 / Q000235:genetics; D016160:Retinoblastoma Protein / Q000378:metabolism*; D013539:Simian virus 40 / Q000276:immunology*
D000952:Antigens, Polyomavirus Transforming; D002087:Butyrates; D008934:Mitogens; D015375:Receptors, Interleukin-2; D016160:Retinoblastoma Protein; D020148:Butyric Acid; D004247:DNA