A potential role for c-jun in cell cycle progression through late G1 and S.
When the level of c-jun mRNA was analyzed in WI-38 human fibroblasts exciting short- and long-term quiescence, two peaks of c-jun mRNA accumulation were found. The first occurred one hour after stimulation and lasted three to five hours, whereas the second occurred at the G1/S border and was coupled to the time of entry to S phase rather than to the time of stimulation. The early peak is well documented and in agreement with the proposed role of c-Jun/AP-1 in mediating cellular responses to receptor-generated signals. The later peak, however, has not been previously reported. Additional follow-up studies showed that late G1/S expression was not solely a phenomenon of cells existing a quiescent state, nor was it restricted only to human cells. Gel retardation studies confirmed that there is AP-1 specific DNA binding activity in nuclear extracts isolated in late G1 and S phase, and that this AP-1 binding activity is due to the presence of Jun protein. An anti-Fos antibody was able to significantly decrease AB-1 binding activity in early G1 extracts, but had no effect on extracts isolated in late G1 and S phase, indicating that the complexes observed in late G1 and S phase are clearly different from those seen in early G1. These studies are among the first to suggest a functional dissociation of c-Jun from c-Fos. Our results identify a new, previously unreported role for c-Jun/AP-1 in regulation of cell cycle progression and mammalian cell growth.
Carter
R
R
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Cosenza
S C
SC
Pena
A
A
Lipson
K
K
Soprano
D R
DR
Soprano
K J
KJ
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016193:G1 Phase; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D016196:S Phase; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA