An altered repertoire of fos/jun (AP-1) at the onset of replicative senescence.
With multiple divisions in culture, normal diploid cells suffer a loss of growth potential that leads to replicative senescence and a finite replicative capacity. Using quantitative RT-PCR, we have monitored mRNA expression levels of c-fos, c-jun, JunB, c-myc, p53, H-ras, and histone H4 during the replicative senescence of human fibroblasts. The earliest and the largest changes in gene expression occurred in c-fos and junB at mid-senescence prior to the first slowing in cell growth rates. The basal level of c-fos mRNA decreased to one-ninth that of the early-passage levels, while junB declined to one-third and c-jun expression remained constant. The decline in the basal c-fos mRNA level in mid-senescence should lead to an increase in Jun/Jun AP-1 homodimers at the expense of Fos/Jun heterodimers and may trigger a cascade of further changes in c-myc, p53, and H-ras expression in late-passage senescent fibroblasts.
Irving
J
J
Department of Biological Chemistry, University of Michigan, Ann Arbor 48105-2007.
Feng
J
J
Wistrom
C
C
Pikaart
M
M
Villeponteau
B
B
D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology*; D016762:Genes, fos; D016758:Genes, jun; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006657:Histones / Q000235:genetics; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors
D006657:Histones; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D007041:Hypoxanthine Phosphoribosyltransferase