Calculation of half-lives of proteins in vivo. Heterogeneity in the rate of degradation of yeast proteins

A method is given for the calculation of half-lives of proteins in vivo from the measurement of the decrease of radioactivity in pulse-labelled proteins with time. This method could be particularly useful for the study of the degradation of proteins in cells that have a low growth rate. The method applied to growing yeast indicates that there are two major classes of protein. The class with low turnover constitutes the bulk of yeast protein and has a half-life of 160 h in a medium with glucose or galactose and of 50 h in a medium with ethanol. The class of proteins with high turnover (half-life between 0.8 and 2.4 hours) represents from 1% of total protein in yeast growing on glucose to 7% in yeast growing on ethanol. It is shown that some proteins which are derepressed during growth on ethanol or induced during growth on galactose are particularly susceptible to degradation in a medium which contains glucose. It is proposed that protein degradation is regulated by a coarse control at the level of protease activity and a fine control on the susceptibility of individual proteins to proteases.This work was supported by a grant from the Comisión Asesora para la Investigación Científica y Técnica. S. L. benefted from a fellowship of the Spanish Ministerio de Educación y Ciencia