A heterogeneous set of urea-insoluble proteins in dividing PC12 pheochromocytoma cells is passed on to at least the generation of great-granddaughter cells.

About 5% of the total cellular protein synthesized in exponentially dividing PC12 pheochromocytoma cells remains insoluble after extractions with aqueous buffer, nonionic detergent, and a strong denaturant, 6M urea. Single- and double-radiolabel pulse-chase labeling experiments with radioactive leucine indicate that for much of the 6 M urea-insoluble protein there is either a lag between its synthesis and deposition in a urea-insoluble compartment and/or the urea-insoluble protein is comparatively stabilized from destruction. Given the doubling time of PC12 cells, much of the long-lived and urea-insoluble protein of PC12 cells is passed on for at least three generations. Electrophoretic analyses show there are many species of long-lived proteins in the 6M urea-insoluble fraction, displayed as a near continuum of subunit molecular weights.