title: Asi1 is an inner nuclear membrane protein that restricts promoter access of two latent transcription factors.
abstract: Stp1 and Stp2 are homologous transcription factors in yeast that are synthesized as latent cytoplasmic precursors with NH2-terminal regulatory domains. In response to extracellular amino acids, the plasma membrane-localized Ssy1-Ptr3-Ssy5 (SPS) sensor endoproteolytically processes Stp1 and Stp2, an event that releases the regulatory domains. The processed forms of Stp1 and Stp2 efficiently target to the nucleus and bind promoters of amino acid permease genes. In this study, we report that Asi1 is an integral component of the inner nuclear membrane that maintains the latent characteristics of unprocessed Stp1 and Stp2. In cells lacking Asi1, full-length forms of Stp1 and Stp2 constitutively induce SPS sensor-regulated genes. The regulatory domains of Stp1 and Stp2 contain a conserved motif that confers Asi1-mediated control when fused to an unrelated DNA-binding protein. Our results indicate that latent precursor forms of Stp1 and Stp2 inefficiently enter the nucleus; however, once there, Asi1 restricts them from binding SPS sensor-regulated promoters. These findings reveal an unanticipated role of inner nuclear membrane proteins in controlling gene expression.
authors.affiliation: Ludwig Institute for Cancer Research, S-171 77 Stockholm, Sweden.
authors.forename: Mirta
authors.initials: M
authors.lastname: Boban
authors.forename: Arezou
authors.initials: A
authors.lastname: Zargari
authors.forename: Claes
authors.initials: C
authors.lastname: Andréasson
authors.forename: Stijn
authors.initials: S
authors.lastname: Heessen
authors.forename: Johan
authors.initials: J
authors.lastname: Thyberg
authors.forename: Per O
authors.initials: PO
authors.lastname: Ljungdahl
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism
chemical_list: C438144:ASI1 protein, S cerevisiae; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C106976:PTR3 protein, S cerevisiae; D016601:RNA-Binding Proteins; C120527:SSY1 protein, S cerevisiae; C074632:STP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C421606:Stp2 protein, S cerevisiae; D014157:Transcription Factors