Growth suppression induced by wild-type p53 protein is accompanied by selective down-regulation of proliferating-cell nuclear antigen expression.
The p53 gene is a frequent target of mutation in a wide variety of human cancers. Previously, it was reported that conditional expression of wild-type p53 protein in a cell line (GM47.23) derived from a human glioblastoma multiform tumor had a negative effect on cell proliferation. We have now investigated the effect that induction of wild-type p53 protein in this cell line has on the expression of the proliferating-cell nuclear antigen gene. The proliferating-cell nuclear antigen gene encodes a nuclear protein that is an auxiliary factor of DNA polymerase delta and part of the DNA replication machinery of the cell. We show that inhibition of cell cycle progression into S-phase after induction of wild-type p53 protein is accompanied by selective down-regulation of proliferating-cell nuclear antigen mRNA and protein expression.
Mercer
W E
WE
Department of Pathology, Temple University School of Medicine, Philadelphia, PA 19140.
Shields
M T
MT
Lin
D
D
Appella
E
E
Ullrich
S J
SJ
D000951:Antigens, Neoplasm / Q000235:genetics; D015152:Blotting, Northern; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D006801:Humans; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D010957:Plasmids; D018809:Proliferating Cell Nuclear Antigen; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D000951:Antigens, Neoplasm; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D012313:RNA