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Protooncogene junB as a target for activin actions
M Hashimoto1, D Gaddy-Kurten, W Vale
1Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, California 92037-1099.
Abstract:
Activin, a member of the transforming growth factor-beta family of peptides, is implicated in the regulation of cell growth and differentiation in a variety of biological systems. We have sought to identify immediate early genes whose altered expression may provide a common nuclear event involved in activin-regulated phenotypic changes in many cell types. In both human K562 myelogenous leukemia and rat PC12 pheochromocytoma cells, activin treatment caused transient transcription-dependent and protein synthesis-independent increases of junB messenger RNA (mRNA) within 1 h, whereas neither c-jun nor c-fos mRNA were inducible. In K562 cells, this selective junB mRNA induction was synergistically augmented by treatment with 12-O-tetradecanoyl phorbol-13-acetate but not affected by forskolin. Furthermore, in PC12 cells, the up-regulation of junB mRNA by activin was observable even after high-dose treatment with 12-O-tetradecanoyl phorbol-13-acetate for 48 h, indicating that junB mRNA expression by activin is independent of both A- and C-kinases. Our report suggests that induction of this ubiquitous gene product may be a critical event shared by a set of activin-responsive tissues.
Insights
Activin rapidly increases junB messenger RNA (mRNA) levels in various cells. This induction is transcription-dependent and occurs independently of protein synthesis, suggesting junB is a key event in activin signaling.
Area of Science:
- Molecular Biology
- Cell Signaling
- Gene Expression
Background:
- Activin, a transforming growth factor-beta peptide, regulates cell growth and differentiation.
- Identifying immediate early genes offers insight into nuclear events driving activin-regulated cellular changes.
Purpose of the Study:
- To identify immediate early genes involved in activin-mediated cellular responses.
- To investigate the role of junB gene expression in activin signaling pathways.
Main Methods:
- Treatment of human K562 and rat PC12 cells with activin.
- Analysis of junB, c-jun, and c-fos messenger RNA (mRNA) levels.
- Assessment of junB induction in the presence of 12-O-tetradecanoyl phorbol-13-acetate and forskolin.
Main Results:
- Activin induced a rapid, transcription-dependent increase in junB mRNA in both cell types within 1 hour.
- Neither c-jun nor c-fos mRNA levels were significantly affected by activin treatment.
- Activin-induced junB mRNA expression was independent of protein synthesis and protein kinase C (PKC) and protein kinase A (PKA) pathways.
Conclusions:
- Activin selectively induces junB mRNA, suggesting its critical role in mediating activin's effects.
- The induction of junB represents a common nuclear event in diverse activin-responsive tissues.
- JunB gene induction by activin is a rapid, transcription-dependent process independent of major signaling kinases.