Control of protein degradation and growth phase in normal and neoplastic cells.
Cells have to double their protein mass in order to divide. Whether this is achieved through increased synthesis (PS), decreased degradation (PD), or a combination of both is still debated. Likewise open are other basic questions: whether, beyond differences relating to growth phase (GP) or rate, reduced PD rates are a general characteristic of neoplastic versus normal cells, conferring to them a definite growth advantage; which mechanisms are operating the PD regulation, if any, during GP transitions, and which ones may be defective in neoplastic cells. Growing liver under conditions of regeneration or development is known to achieve a net protein accumulation thanks to increased PS, and particularly, to decreased PD rates, as compared with the adult, steady-state tissue; the level of lysosomal proteinase (LP) activities is reduced; in the regenerating liver this reduction has been located in cycling hepatocytes. AH-130 Yoshida ascites hepatoma cells effect the transition from log to stationary GP by concurrently reducing PS and accelerating PD (slow turnover protein pool); while PD is virtually not affected by lysosomal inhibitors (LI) in growing cells, the extra PD in resting cells is all inhibitable; there is no regulation of LP levels over this GP transition, which is due to depletion of oxygen and nutrients. GP transitions in normal 3T3 cells are also coupled with regulations of both PS and PD, the extra PD in quiescent cells being all suppressible by LI. Quiescence of 3T3 cells, due to depletion of growth factors, is associated with a marked elevation of some LP activities.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000378:metabolism*
D011506:Proteins