Degradation of intracellular endogenous proteins following serum deprivation in mammalian cell cultures: theoretical considerations of the role of very-fast turnover proteins in growth regulation.
This paper discusses the way in which serum deprivation affects the turnover of nascent or newly synthesised proteins in mammalian cells. A theoretical treatment of their turnover relative to changes in rate of protein synthesis and the turnover of existing or "resident" proteins is presented. Previous experimental work has not seriously addressed this question because the pulses of radiolabelling of proteins have been too long to identify the very-fast turnover population (Wheatley et al., 1980; Bohley, 1987). Logically one would expect cell growth rate to be regulated by the rate at which new proteins become incorporated into the cell within the first 30 min of their existence. This requires their successful integration at what we will refer to as the "growing point", recognizing that at any time there may be thousands of such sites. Growth is a simple term betraying the complexity of the processes involved--synthesis, processing, sorting, targeting, and stabilization of macromolecules, and their successful integration into functional assemblies at appropriate locations. Turnover of the truly short-lived, very-fast turnover proteins at the "growing point" is affected by serum adjustment, but it is not the only change since synthetic rate quickly responds, as also does the turnover rate of long-lived proteins. Our theoretical discussion will relate to recent findings in 3T3 and HeLa cell cultures after serum modulation, lines with quite different dependencies on serum growth factors.
Wheatley
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DN
Department of Pathology, Aberdeen, Scotland, U.K.
Yin
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D016475:3T3 Cells; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002452:Cell Count; D002455:Cell Division; D002478:Cells, Cultured; D003470:Culture Media; D016326:Extracellular Matrix Proteins; D006133:Growth Substances / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007930:Leucine / Q000378:metabolism; D051379:Mice; D014176:Protein Biosynthesis
D001798:Blood Proteins; D003470:Culture Media; D016326:Extracellular Matrix Proteins; D006133:Growth Substances; D007930:Leucine