Crm1 (XpoI) dependent nuclear export of the budding yeast transcription factor yAP-1 is sensitive to oxidative stress.
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.
Kuge
S
S
Department of Microbiology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. skuge@ims.u-tokyo.ac.jp
Toda
T
T
Iizuka
N
N
Nomoto
A
A
D001426:Bacterial Proteins; D050976:Basic-Leucine Zipper Transcription Factors; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism*; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D005656:Fungal Proteins; D015966:Gene Expression Regulation, Fungal; D017930:Genes, Reporter; D028884:Karyopherins; D008954:Models, Biological; D018384:Oxidative Stress; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D000097606:Exportin 1 Protein
D001426:Bacterial Proteins; D050976:Basic-Leucine Zipper Transcription Factors; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005656:Fungal Proteins; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D029702:Schizosaccharomyces pombe Proteins; D018808:Transcription Factor AP-1; D000097606:Exportin 1 Protein; C105096:Pap1 protein, S pombe; C100898:nes protein, Staphylococcus aureus