Activation of AP-1-Dependent Transcription by a Truncated Translation Initiation Factor
Open Access
- 1 November 2005
- journal article
- research article
- Published by American Society for Microbiology in Eukaryotic Cell
- Vol. 4 (11), 1840-1850
- https://doi.org/10.1128/ec.4.11.1840-1850.2005
Abstract
Int6/eIF3e is a highly conserved subunit of eukaryotic translation initiation factor 3 (eIF3) that has also been reported to interact with subunits of the proteasome and the COP9 signalosome. Overexpression of full-length Int6 or a 13-kDa C-terminal fragment, Int6CT, in the fission yeast Schizosaccharomyces pombe causes multidrug resistance that requires the otherwise inessential AP-1 transcription factor Pap1. Here we show for the first time that Int6CT acts to increase the transcriptional activity of Pap1. Microarray hybridization data indicate that Int6CT overexpression resulted in the up-regulation of 67 genes; this expression profile closely matched that of cells overexpressing Pap1. Analysis of the upstream regulatory sequences of these genes showed that the majority contained AP-1 consensus binding sites. Partial defects in ubiquitin-dependent proteolysis have been suggested to confer Pap1-dependent multidrug resistance, but no such defect was seen on Int6CT overexpression. Indeed, none of the previously identified interactions of endogenous Int6 was required for the activation of Pap1 transcription described here. Moreover, Int6CT-induced activation of Pap1-responsive gene expression was independent of the ability of Pap1 to undergo a redox-regulated conformational change which mediates its relocalization to the nucleus and expression of oxidative stress response genes. Int6CT therefore activates Pap1-dependent transcription by a novel mechanism.Keywords
This publication has 42 references indexed in Scilit:
- Cell cycle-related variation in subcellular localization of eIF3e/INT6 in human fibroblastsCell Proliferation, 2004
- The transcription factor Pap1/Caf3 plays a central role in the determination of caffeine resistance in Schizosaccharomyces pombeMolecular Genetics and Genomics, 2004
- Adenoviral delivery of A-FOS, an AP-1 dominant negative, selectively inhibits drug resistance in two human cancer cell linesCancer Gene Therapy, 2002
- Fission Yeast Homolog of Murine Int-6 Protein, Encoded by Mouse Mammary Tumor Virus Integration Site, Is Associated with the Conserved Core Subunits of Eukaryotic Translation Initiation Factor 3Published by Elsevier BV ,2001
- Arabidopsis eIF3e (INT-6) Associates with Both eIF3c and the COP9 Signalosome Subunit CSN7Journal of Biological Chemistry, 2001
- The Translation Initiation Factor eIF3-p48 Subunit Is Encoded byint-6, a Site of Frequent Integration by the Mouse Mammary Tumor Virus GenomeJournal of Biological Chemistry, 1997
- Thiamine-repressible expression vectors pREP and pRIP for fission yeastGene, 1993
- Fission yeast genes that confer resistance to staurosporine encode an AP-1-like transcription factor and a protein kinase related to the mammalian ERK1/MAP2 and budding yeast FUS3 and KSS1 kinases.Genes & Development, 1991
- [56] Molecular genetic analysis of fission yeast Schizosaccharomyces pombeMethods in enzymology, 1991
- Expression of the SV40 promoter in fission yeast: Identification and characterization of an AP-1-like factorCell, 1988