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Originally published In Press as doi:10.1074/jbc.M609201200 on November 3, 2006

J. Biol. Chem., Vol. 282, Issue 1, 594-605, January 5, 2007
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Inner Nuclear Membrane Proteins Asi1, Asi2, and Asi3 Function in Concert to Maintain the Latent Properties of Transcription Factors Stp1 and Stp2*Formula

Arezou Zargari{ddagger}1, Mirta Boban{ddagger}1, Stijn Heessen{ddagger}, Claes Andréasson{ddagger}, Johan Thyberg§, and Per O. Ljungdahl{ddagger}2

From the {ddagger}Ludwig Institute for Cancer Research and the §Department of Cell and Molecular Biology, Karolinska Institute, S-17177 Stockholm, Sweden

In yeast the homologous transcription factors Stp1 and Stp2 are synthesized as latent cytoplasmic precursors with N-terminal regulatory domains. In response to extracellular amino acids the regulatory domains are endoproteolytically excised by the plasma membrane-localized SPS sensor. The processed forms of Stp1 and Stp2 efficiently enter the nucleus and induce expression of amino acid permease genes. We recently reported that the inner nuclear membrane protein Asi1 is required to prevent unprocessed forms of Stp1 and Stp2, which ectopically enter the nucleus, from binding SPS sensor-regulated promoters. Here we show that Asi3, an Asi1 homolog, and Asi2 are integral proteins of the inner nuclear membrane that function in concert with Asi1. In cells lacking any of the three Asi proteins, unprocessed full-length forms of Stp1 and Stp2 constitutively induce SPS sensor-regulated genes. Our results demonstrate that the Asi proteins ensure the fidelity of SPS sensor signaling by maintaining the dormant, or repressed state, of gene expression in the absence of inducing signals. This study documents additional components of a novel mechanism controlling transcription in eukaryotic cells.


Received for publication, September 28, 2006 , and in revised form, November 3, 2006.

* This work was supported by grants from the Ludwig Institute for Cancer Research (to P. O. L.) and the Swedish Research Council (to J. T. and P. O. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Formula The on-line version of this article (available at http://www.jbc.org) contains data, additional references, and Table S1.

1 Both authors contributed equally to this work.

2 To whom correspondence should be addressed: Box 240, S-17177 Stockholm, Sweden. Tel.: 46-8-524-87108; Fax: 46-8-33-28-12; E-mail: plju{at}licr.ki.se.


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GeneticsHome page
M. Boban and P. O. Ljungdahl
Dal81 Enhances Stp1- and Stp2-Dependent Transcription Necessitating Negative Modulation by Inner Nuclear Membrane Protein Asi1 in Saccharomyces cerevisiae
Genetics, August 1, 2007; 176(4): 2087 - 2097.
[Abstract] [Full Text] [PDF]




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