Restriction Point Control of Cell Growth by a Labile Protein: Evidence for Increased Stability in Transformed Cells

It has been proposed that animal cells must accumulate a labile protein(s) before they can pass the restriction (R) point in the G1phase of the cell cycle [Rossow, P. W., Riddle, V. G. H. & Pardee, A. B. (1979) Proc. Natl. Acad. Sci. USA 76, 4446-4450]. Here, we present evidence that this R prot...

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Veröffentlicht in:Proceedings of the National Academy of Sciences of the United States of America. - National Academy of Sciences of the United States of America. - 79(1982), 2, Seite 436-440
1. Verfasser: Campisi, Judith (VerfasserIn)
Weitere Verfasser: Medrano, Estela E., Morreo, Gail, Pardee, Arthur B.
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 1982
Zugriff auf das übergeordnete Werk:Proceedings of the National Academy of Sciences of the United States of America
Schlagworte:Cell Biology Animal Cells Transformation Protein Degradation Cell Cycle Growth Control Biological sciences Physical sciences
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520 |a It has been proposed that animal cells must accumulate a labile protein(s) before they can pass the restriction (R) point in the G1phase of the cell cycle [Rossow, P. W., Riddle, V. G. H. & Pardee, A. B. (1979) Proc. Natl. Acad. Sci. USA 76, 4446-4450]. Here, we present evidence that this R protein acquires increased stability in transformed 3T3 cells, thereby allowing these cells to continue growth under conditions that arrest untransformed cells. Low doses of cycloheximide or histidinol drastically reduced the rate at which normal 3T3 (A31) fibroblasts in early G1could enter DNA synthesis. These drugs had less effect on entry of two tumorigenic A31 derivatives, BPA31 and SVA31, into S, although measurement of [3H]leucine incorporation showed that the inhibitors were equally effective in the three cell lines. The hypothesis is that the transformed lines are less sensitive because moderate inhibition of their R protein synthesis is compensated by lower rates of protein degradation. To test this idea, we completely inhibited cytoplasmic protein synthesis for several hours shortly before A31 and BPA31 cells had reached the R point. After removal of inhibitor, A31 cells showed delays in the onset of S that were in excess of the inhibitor pulse, consistent with decay of labile protein during the pulse. BPA31 cells showed no excess delays, suggesting a much more stable R protein. The half-life of the R protein was estimated as 2.5 hr in A31 cells, indicating that, in these cells, R protein synthesis starts at the beginning of G1. In the BPA31 cells, the R protein showed no signs of decay for at least 8 hr. 
650 4 |a Cell Biology 
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650 4 |a Transformation 
650 4 |a Protein Degradation 
650 4 |a Cell Cycle 
650 4 |a Growth Control 
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650 4 |a Biological sciences  |x Biology  |x Cytology  |x Cell biology  |x Cells  |x Cultured cells  |x Cell lines 
650 4 |a Biological sciences  |x Biology  |x Genetics  |x Molecular genetics  |x Genetic translation  |x Protein synthesis 
650 4 |a Biological sciences  |x Biology  |x Cytology  |x Cell biology  |x Cells  |x Animal cells 
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650 4 |a Biological sciences  |x Biology  |x Cytology  |x Cell biology  |x Cell physiology  |x Cell growth 
650 4 |a Physical sciences  |x Chemistry  |x Chemical compounds  |x Chemicals  |x Acids  |x Nucleic acids  |x DNA 
650 4 |a Biological sciences  |x Biology  |x Cytology  |x Cell biology  |x Cells  |x Cultured cells  |x Cell lines  |x Transformed cell line 
650 4 |a Physical sciences  |x Physics  |x Microphysics  |x Atomic physics  |x Half lives 
650 4 |a Biological sciences  |x Biology  |x Cytology  |x Cell biology  |x Cells  |x Cultured cells 
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700 1 |a Medrano, Estela E.  |e verfasserin  |4 aut 
700 1 |a Morreo, Gail  |e verfasserin  |4 aut 
700 1 |a Pardee, Arthur B.  |e verfasserin  |4 aut 
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