Synthesis of labile, serum-dependent protein in early G1 controls animal cell growth - PubMed (original) (raw)

Synthesis of labile, serum-dependent protein in early G1 controls animal cell growth

P W Rossow et al. Proc Natl Acad Sci U S A. 1979 Sep.

Abstract

We present a model to account for several major observations on growth control of animal cells in culture. This model is tested by means of kinetic experiments which show that exponentially growing animal cells whose ability to synthesize total protein has been inhibited with cycloheximide (by up to 70%) grow at rates approximately proportional to their rates of protein synthesis. However, virtually the entire elongation of the cell cycle occurs in the part of the G(1) phase that depends on a high concentration of serum in the medium. This part of the cycle has earlier been suggested to lie prior to the restriction point-i.e., the point beyond the main regulatory processes of G(1). The remainder of the cycle, from restriction point to mitosis, is markedly insensitive to these concentrations of cycloheximide as well as to growth regulation. We quantitatively account for the specific lengthening of that part of the cycle involved in growth regulation by assuming that cells must accumulate a specific protein in a critical amount before they can proceed beyond the restriction point. The lability of this protein (half-life about 2 hr) makes its accumulation unusually sensitive to inhibition of total protein synthesis by cycloheximide. Its production appears to depend on growth factors provided by serum. The model can also account for greater variations of G(1) durations as the growth of cell populations is made slower. It also predicts two sorts of quiescence: one of cells slowly traversing G(1), in slightly suboptimal conditions; the other of cells that enter G(0) under inadequate conditions. Transformation of different sorts could create cells with altered variables for initiation, synthesis, or inactivation of the regulatory protein or could altogether eliminate the need for the protein.

PubMed Disclaimer

Cited by

Cell cycle regulated phosphorylation of RPA-32 occurs within the replication initiation complex.
Fotedar R, Roberts JM. Fotedar R, et al. EMBO J. 1992 Jun;11(6):2177-87. doi: 10.1002/j.1460-2075.1992.tb05277.x. EMBO J. 1992. PMID: 1318194 Free PMC article.
Intracellular K+ and the mitogenic response of 3T3 cells to peptide factors in serum-free medium.
Lopez-Rivas A, Adelberg EA, Rozengurt E. Lopez-Rivas A, et al. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6275-9. doi: 10.1073/pnas.79.20.6275. Proc Natl Acad Sci U S A. 1982. PMID: 6755467 Free PMC article.
Post-transcriptional control of the onset of DNA synthesis by an insulin-like growth factor.
Campisi J, Pardee AB. Campisi J, et al. Mol Cell Biol. 1984 Sep;4(9):1807-14. doi: 10.1128/mcb.4.9.1807-1814.1984. Mol Cell Biol. 1984. PMID: 6387447 Free PMC article.
Control of thymidine kinase mRNA during the cell cycle.
Coppock DL, Pardee AB. Coppock DL, et al. Mol Cell Biol. 1987 Aug;7(8):2925-32. doi: 10.1128/mcb.7.8.2925-2932.1987. Mol Cell Biol. 1987. PMID: 3670299 Free PMC article.
Topoisomerase-specific drug sensitivity in relation to cell cycle progression.
Chow KC, Ross WE. Chow KC, et al. Mol Cell Biol. 1987 Sep;7(9):3119-23. doi: 10.1128/mcb.7.9.3119-3123.1987. Mol Cell Biol. 1987. PMID: 2823120 Free PMC article.

References

1. J Cell Biol. 1976 Oct;71(1):172-81 - PubMed
1. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3937-41 - PubMed
1. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1804-8 - PubMed
1. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1633-7 - PubMed
1. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3745-9 - PubMed

Synthesis of labile, serum-dependent protein in early G1 controls animal cell growth - PubMed (original) (raw)