Serum deprivation and the turnover of short-, medium- and long-lived proteins in 3T3 and HeLa S-3 cells.

Protein turnover in serum-deprived Swiss 3T3(U) untransformed and 3T3(T) transformed cells was comprehensively studied. When 3T3(U) cells were cultured in 0.2% serum medium, protein synthesis fell to 28% of the control value by 48 h, but took at least 12 h to become manifest. Meanwhile the rates of degradation of medium- and long-lived proteins were increasing, with a 1.65-fold increase in degradation of the former within 2 h, and the turnover of long-lived proteins doubling in 24 h. A significant increase in the degradation of truly short-lived proteins was not apparent until 24 h of deprivation. After serum restoration in cultures deprived of serum for 24 h, protein synthesis increased from 25 to 40% of the control values within 1 h, reaching 93% by 24 h. The rate of medium-lived protein degradation in 3T3(U) cells quickly returned to control levels, and that of long-lived proteins fell to less than control levels by 3 h, decreasing to 67% by 24 h. This contrasted with short-lived protein turnover, which remained at the same level as the cells kept in 0.2% serum for a further 24 h. The turnover of medium- and long-lived proteins is initially more important than short-lived proteins in growth regulation following the removal of growth factors.