Control of fibroblast senescence and activation of programmed cell death.
We have characterized a nuclear phosphoprotein of 57 kda, statin, found only in nonproliferating cells of both quiescent and senescent natures. Emerging results suggest that statin may function as a sequester to block the early G1 phase phosphorylation for the RB protein. A second protein, terminin, undergoes senescence-specific posttranslational modification from 90 to 60 kda, and further death-specific conversion from 60 to 30 kda. We also found that apoptotic mouse 3T3 fibroblasts express c-fos, c-myc, c-jun, and cdc2, as well as the upregulation of RB phosphorylation and BrdU incorporation, just before final DNA fragmentation and death. It seems that en route to death, cells re-enter the cell-cycle transverse and experience early G1 and part of S Phase; however, this cycling event is an abortive one. In contrast, senescent fibroblasts are resistant to the initiation of the death program, since they are unable to enter cell cycle traverse. Long-term serial passaging of normal human fibroblasts may be inadvertently selecting those, while termed as senescent, are also specialized survivors, and thus a good culture model to study both the control of permanent departure from cell cycle traverse and the mechanism underlying the survival or antideath cellular program.
Wang
E
E
Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis, Jewish General Hospital, Montréal, Québec, Canada.
Lee
M J
MJ
Pandey
S
S
D000818:Animals; D016923:Cell Death / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D010641:Phenotype