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PMID: 16735580 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Asi1 is an inner nuclear membrane protein that restricts promoter access of two latent transcription factors.

The Journal of cell biology ·Vol. 173 ·No. 5 ·2006-06-05 ·Pages 695-707

Boban M, Zargari A, Andréasson C, Heessen S, Thyberg J, Ljungdahl PO

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.

MeSH Terms
Amino Acid Sequence Carrier Proteins/metabolism DNA-Binding Proteins/drug effects,metabolism Gene Expression Regulation, Fungal Intracellular Signaling Peptides and Proteins Membrane Proteins/genetics,metabolism,pharmacology Molecular Sequence Data Multiprotein Complexes/metabolism Mutation Nuclear Envelope/metabolism Nuclear Proteins/drug effects,metabolism Promoter Regions, Genetic/physiology RNA-Binding Proteins/drug effects,metabolism Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins/drug effects,genetics,metabolism,pharmacology Transcription Factors/drug effects,metabolism
Chemicals
ASI1 protein, S cerevisiae Carrier Proteins DNA-Binding Proteins Intracellular Signaling Peptides and Proteins Membrane Proteins Multiprotein Complexes Nuclear Proteins PTR3 protein, S cerevisiae RNA-Binding Proteins SSY1 protein, S cerevisiae STP1 protein, S cerevisiae Saccharomyces cerevisiae Proteins Stp2 protein, S cerevisiae Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Boban Mirta
Ludwig Institute for Cancer Research, S-171 77 Stockholm, Sweden.
Zargari Arezou
Andréasson Claes
Heessen Stijn
Thyberg Johan
Ljungdahl Per O
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
Published
2006-06-05
Epub
2006-00-30
Pages
695-707
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2063887
Subset
IM
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