Regulation of Protein Degradation in Neoplastic Cells
Changes in the overall rate of cell protein degradation (PD) were included by Hershko and co-workers in 19711 among the elements of the “pleiotypic response”, which was categorized as “positive” if associated with growth stimulation or “negative” if accompanying growth suppression. Protein turnover modulations were thus regarded as instrumental in effecting growth-phase transitions. In 1977 Warburton and Poole2 analyzed the relationship between cell growth and PD rates in tissue cultures exposed to serum deprivation or other manipulations. Moreover, in 1977 Gunn et al.3 reported that basal PD rates in various transformed cells were lower than in their normal counterparts, hypothesizing that a reduction in intracellular proteolysis could play a role in neoplastic growth. Since then, many methodological advances have been developed to analyze PD in tissues or cells, particularly in tissue cultures. Nevertheless, studies on the relationship between cell protein turnover rates and growth or neoplastic transformation have generally relied on experimental models not adequately defined in terms of growth properties and kinetics, not to mention the rather crude tools often used to elicit growth-phase transitions.
KeywordsAdenine Triglyceride Glucagon Thymidine Purine
Unable to display preview. Download preview PDF.
- 1.A. Hershko, P. Mamont, R. Shields and G. M. Tomkins, Pleiotypic response, Nature 232:206 (1971).Google Scholar
- 5.F. M. Baccino, M. Messina, M. Musi, and L. Tessitore, Regulation of cell protein turnover and proteinase activities in relation to growth in: “Recent trends in Chemical Carcinogenesis”, P. Pani, F. Feo, and A. Columbano, eds., ESA, Cagliari (1982).Google Scholar
- 10.F. J. Ballard, Regulation of intracellular protein breakdown with special reference to cultured cells, in: “Lysosomes: their Role in Protein Breakdown”, H. Glaumann and F. J. Ballard, eds., Academic Press, London (1987).Google Scholar
- 11.O. A. Scornick and V. Botbol, Protein metabolism and liver growth, in: “Lysosomes: their Role in Protein Breakdown”, H. Glaumann and F. J. Ballard, eds., Academic Press, London (1987).Google Scholar
- 15.A. Anastasi and R. T. Dean, Regulation of protein degradation in fibroblasts, in: “Intracellular Protein Catabolism”, E. A. Khairallah, J. S. Bond, and J. W. C. Bird, eds., Alan R. Liss, New York, (1985).Google Scholar
- 17.J. S. Amenta, J. Mehta and F. M. Baccino, Proteolysis associated with thymidine-induced selective cell death in L-cell cultures, this book.Google Scholar
- 19.L. Tessitore, G. Bonelli, G. Cecchini, R. Autelli, J. S. Amenta and F. M. Baccino, Regulation of protein turnover vs. growth state. II. Studies on the mechanisms of initiation of acidic vacuolar proteolysis in cells of stationary ascitic hepatoma, Biochem. J. in press (1988).Google Scholar
- 20.U. Pfeifer, L. Tessitore, G. Bonelli and F. M. Baccino, Regulation of protein turnover versus growth state. III, Growth cessation is associated with activation of autophagy in Yoshida ascites hepatoma AH-130, submitted (1988).Google Scholar
- 25.J. C. Waterlow, Protein turnover with special reference to man, Quart. J. Exp. Physiol. 69:409 (1984).Google Scholar
- 27.M. Olivotto, R. Caldini, M. Chevanne and M. G. Cipolleschi, The respiration-linked limiting step of tumor cell transition from the non-cycling to the cycling state: its inhibition by oxidizable substrates and its relationships to purine metabolism, J. Cell. Physiol. 116:149 (1983).PubMedCrossRefGoogle Scholar