Cell-shape-dependent modulation of p52(PAI-1) gene expression involves a secondary response pathway

Expression of the rat p52(PAI-1) gene is positively regulated by agents that influence cellular microfilament organization and/or cell-to-substrate adhesion [e.g. cytochalasin D (CD) and sodium n-butyrate (NaB)] [Higgins, Chaudhari and Ryan (1991) Biochem. J. 273, 651-658; Higgins, Ryan and Providen...

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Bibliographic Details
Published in:Biochemical journal 1995-03, Vol.306 ( Pt 2) (2), p.497-504
Main Authors: Higgins, P J, Staiano-Coico, L, Ryan, M P
Format: Article
Language:English
Subjects:
Butyrates - pharmacology
Butyric Acid
Cell Line
Cell Line, Transformed
Cell Size - drug effects
Cell Size - genetics
Cycloheximide - pharmacology
Cytochalasin D - pharmacology
Dactinomycin - pharmacology
Flow Cytometry
Fluorescent Antibody Technique
Gene Expression - drug effects
Genes, ras
Kidney
Kinetics
Plasminogen Activator Inhibitor 1 - genetics
Protein Biosynthesis
RNA, Messenger - biosynthesis
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Summary:Expression of the rat p52(PAI-1) gene is positively regulated by agents that influence cellular microfilament organization and/or cell-to-substrate adhesion [e.g. cytochalasin D (CD) and sodium n-butyrate (NaB)] [Higgins, Chaudhari and Ryan (1991) Biochem. J. 273, 651-658; Higgins, Ryan and Providence (1994) J. Cell. Physiol. 159, 187-195]. As shape-responsive genes may be subject to inducer-specific controls, the biochemical mechanisms underlying the shape-dependent pathway of p52(PAI-1) gene regulation were examined in v-ras-transformed rat kidney (KNRK) cells. NaB and/or CD effectively stimulated p52(PAI-1) run-off transcription and augmented de novo p52(PAI-1) mRNA and protein synthesis in KNRK cells; induction at both the mRNA and protein levels was inhibited by actinomycin D. Pretreatment with cycloheximide (CX) markedly attenuated NaB- and/or CD-stimulated p52(PAI-1) expression. CX alone, however, induced low levels of p52(PAI-1) mRNA; increased p52(PAI-1) protein synthesis was evident after release of KNRK cells from CX blockade. Such CX-mediated induction was also sensitive to actinomycin D. Full stimulation of p52(PAI-1) expression in KNRK cells in response to the shape modulators NaB and/or CD involves transcriptional activation of the p52(PAI-1) gene, requires de novo RNA synthesis and occurs through a secondary-response (i.e. protein-synthesis-dependent) pathway.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj3060497