Down-regulation of the stathmin/Op18 and FKBP25 genes following p53 induction.
The p53 tumor suppressor protein can function as an activator and a repressor of gene transcription. Currently, the mechanism of transcriptional repression by p53 is poorly understood. To aid in clarifying this mechanism, we carried out studies designed to identify specific target genes that are down-regulated following p53 induction. Among the negative p53-response genes revealed by our screening protocols are those encoding stathmin (Op18), a tubulin-associated protein implicated in cell signaling pathways, and an FK506/rapamycin-binding protein, FKBP25. Stathmin and FKBP25 exhibit decreased expression in both human and murine immortalized and transformed cell lines following induction of wild-type p53 by several stimuli that result in DNA damage. Candidate p53-repressed genes such as these provide the necessary markers to delineate the mechanism and biological consequences of transcriptional repression mediated by p53.
Ahn
J
J
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennyslvania, PA 19104-6069, USA.
Murphy
M
M
Kratowicz
S
S
Wang
A
A
Levine
A J
AJ
George
D L
DL
D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D020104:Immunophilins / Q000235:genetics*; D051379:Mice; D008868:Microtubule Proteins; D010750:Phosphoproteins / Q000235:genetics*; D050777:Stathmin; D022021:Tacrolimus Binding Proteins; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C489567:Fkbp3 protein, mouse; D008868:Microtubule Proteins; D010750:Phosphoproteins; C493995:STMN1 protein, human; D050777:Stathmin; C493994:Stmn1 protein, mouse; D016159:Tumor Suppressor Protein p53; C074856:FKBP3 protein, human; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins