The growth inhibition in Friend erythroleukemia cells induces cycling of preexisting nonhistone proteins.
The present investigation performed on Friend erythroleukemia cells provides evidence that the cellular reprogramming associated with transition of the cells from the growing to the resting state is accompanied by an intranuclear cycling of preexisting proteins migrating from the cytoplasm. The model system developed for this study affords an opportunity to follow these events in a conveniently short period. The flow microfluorometric analysis revealed that, with respect to DNA content, the quiescent nuclei exhibit distribution in G1, S and G2 phases, as do the nuclei of the control, exponentially growing cells. It was found further that the induction of quiescence arouses two waves of migration of preexisting cytoplasmic proteins toward the nucleus: an early one, during the transition to quiescence clearly showing density dependence, and a late one, in the established resting state. While the early-cycled proteins are undetectable in mass and once they have reached the nucleus have a short life time and, thus, could be considered as regulatory molecules, the late-cycled proteins accumulate within the nucleus and are associated most probably with structural reorganization of the resting nuclei; moreover, the late-cycled nonhistone proteins were found localized, at least partly, in the nuclear protein matrix structure. Control experiments confirmed that the early and late-cycled proteins have been synthesized in the cytoplasm in the proliferative state but are cycled intranuclearly only if the resting state has been induced. When finally the resting cells were stimulated to proliferate, the accumulated presynthesized and newly synthesized nonhistone proteins undergo a rapid degradation which suggests that the new cellular programme may require a complete elimination of the 'resting' nonhistone proteins.
D000818:Animals; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005434:Flow Cytometry; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D007942:Leukemia, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D009363:Neoplasm Proteins