S Kuge1, T Toda, N Iizuka, A Nomoto. 1. Department of Microbiology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. skuge@ims.u-tokyo.ac.jp
Abstract
BACKGROUND: The yAP-1 transcription factor is crucial for the oxidative stress response of the budding yeast Saccharomyces cerevisiae; its activity is induced in response to oxidative stress, and as a consequence the expression of a number of target genes is enhanced. We have shown previously that yAP-1 is mainly found in the cytoplasm, but that upon the imposition of oxidative stress it localizes to the nucleus. In this study, we addressed the mechanism through which yAP-1 nuclear localization is regulated. RESULTS: Here we show that yAP-1 localization is mediated by active export from the nucleus, resulting from the activity of Crm1 (XpoI), a conserved protein that functions as an export receptor which recognizes the nuclear export signal (NES). When Crm1 expression was repressed, yAP-1 was localized in the nucleus and induced the expression of a yAP-1 dependent target gene. Our results also suggest that the cysteine rich domain (CRD), at the C-terminus of yAP-1, functions as an export recognition sequence. yAP-1 and Crm1 interact in vivo and this interaction is reduced in response to oxidative stress. CONCLUSIONS: These results suggest a novel regulatory mechanism of nucleocytoplasmic transport which is dependent upon a redox sensitive nuclear export pathway.
BACKGROUND: The yAP-1 transcription factor is crucial for the oxidative stress response of the budding yeastSaccharomyces cerevisiae; its activity is induced in response to oxidative stress, and as a consequence the expression of a number of target genes is enhanced. We have shown previously that yAP-1 is mainly found in the cytoplasm, but that upon the imposition of oxidative stress it localizes to the nucleus. In this study, we addressed the mechanism through which yAP-1 nuclear localization is regulated. RESULTS: Here we show that yAP-1 localization is mediated by active export from the nucleus, resulting from the activity of Crm1 (XpoI), a conserved protein that functions as an export receptor which recognizes the nuclear export signal (NES). When Crm1 expression was repressed, yAP-1 was localized in the nucleus and induced the expression of a yAP-1 dependent target gene. Our results also suggest that the cysteine rich domain (CRD), at the C-terminus of yAP-1, functions as an export recognition sequence. yAP-1 and Crm1 interact in vivo and this interaction is reduced in response to oxidative stress. CONCLUSIONS: These results suggest a novel regulatory mechanism of nucleocytoplasmic transport which is dependent upon a redox sensitive nuclear export pathway.
Authors: Susan M Kraemer; David A Goldstrohm; Ann Berger; Susan Hankey; Sherry A Rovinsky; W Scott Moye-Rowley; Laurie A Stargell Journal: Eukaryot Cell Date: 2006-07