[Trigger approach to proliferation, aging, and immortalization of animal cells].
It is proposed that the expression regulation system of a nuclear protooncogene behaves as a trigger, its mRNA stability depending on growth factors. If cells can proliferate, the system tends towards one of stable stationary states. Since transcription does not take place during mitosis, the amount of protooncogene products is rapidly decreased (they are extremely unstable). When mitosis terminates, the system can tend towards either the former state (i.e. it recycles) or another stable stationary state. The system can not pass from the latter state to the former one, if even growth factors are added, i.e. such a cell is terminally differentiated. A cell population should have a limited doubling potential. If a nuclear protooncogene acquires a foreign promoter, then the system will have a single stable stationary state; such cells are unable to become terminally differentiated. If the gene loses mRNA-destabilizing sequences, then the terminal differentiation probability will become far less than formerly. Mutations of genes for proteins digesting specifically the protooncogene mRNAs should lead to the same effect. Any of the events should cause cell immortalization.
Romanchikov
Iu M
IuM
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D016922:Cellular Senescence; D015870:Gene Expression; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D012333:RNA, Messenger
Triggernyĭ podkhod k proliferatsii, stareniiu i immortalizatsii kletokzhivotnykh.