title: Asr1p, a novel yeast ring/PHD finger protein, signals alcohol stress to the nucleus.
abstract: During fermentation, yeast cells are exposed to increasing amounts of alcohol, which is stressful and affects both growth and viability. On the molecular level, numerous aspects of alcohol stress signaling remain unresolved. We have identified a novel yeast Ring/PHD finger protein that constitutively shuttles between nucleus and cytoplasm but accumulates in the nucleus upon exposure to ethanol, 2-propanol, or 1-butanol. Subcellular localization of this protein is not altered by osmotic, oxidative, or heat stress or during nitrogen or glucose starvation. Because of its exclusive sensitivity to environmental alcohol, the protein was called Asr1p for Alcohol Sensitive Ring/PHD finger 1 protein. Nuclear accumulation of Asr1p is rapid, reversible, and requires a functional Ran/Gsp1p gradient. Asr1p contains two N terminally located leucine-rich nuclear export sequences (NES) required for nuclear export. Consistently, it accumulates in the nucleus of xpo1-1 cells at restrictive temperature and forms a trimeric complex with the exportin Xpo1p and Ran-GTP. Deletion of ASR1 leads to sensitivity in growth on medium containing alcohol or detergent, consistent with a function of Asr1p in alcohol-related signaling. Asr1p is the first reported protein that changes its subcellular localization specifically upon exposure to alcohol and therefore represents a key element in the analysis of alcohol-responsive signaling.
authors.affiliation: Universität des Saarlandes, Medizinische Biochemie und Molekularbiologie, Gebäude 44, D-66421 Homburg/Saar, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Betz
authors.forename: Gabriel
authors.initials: G
authors.lastname: Schlenstedt
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Bailer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000438:Alcohols / Q000378:metabolism*; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000502:physiology*; D049452:Green Fluorescent Proteins; D028884:Karyopherins / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013696:Temperature; D013997:Time Factors; D000097606:Exportin 1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000438:Alcohols; D002352:Carrier Proteins; D005656:Fungal Proteins; D049452:Green Fluorescent Proteins; D028884:Karyopherins; D008164:Luminescent Proteins; D020559:Monomeric GTP-Binding Proteins; D009687:Nuclear Proteins; D010100:Oxygen; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D000097606:Exportin 1 Protein; C488254:Asr1 protein, S cerevisiae; C080324:GSP1 protein, S cerevisiae