This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Andréasson, C. Articles by Ljungdahl, P. O. Search for Related Content PubMed PubMed Citation Articles by Andréasson, C. Articles by Ljungdahl, P. O.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2004, p. 7503-7513, Vol. 24, No. 17
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.17.7503-7513.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The N-Terminal Regulatory Domain of Stp1p Is Modular and, Fused to an Artificial Transcription Factor, Confers Full Ssy1p-Ptr3p-Ssy5p Sensor Control

Ludwig Institute for Cancer Research, Stockholm, Sweden

Received 8 March 2004/ Returned for modification 26 April 2004/ Accepted 10 June 2004

Stp1p and Stp2p are homologous and redundant transcription factors that are synthesized as latent cytoplasmic proteins with N-terminal regulatory domains. In response to extracellular amino acids, the plasma membrane-localized Ssy1p-Ptr3p-Ssy5p (SPS) sensor induces an endoproteolytic processing event that cleaves away the N-terminal regulatory domains. The shorter forms of Stp1p and Stp2p are targeted to the nucleus, where they bind and activate the transcription of amino acid permease genes. A novel genetic screen, specifically designed to search for rare mutations that affect the SPS-sensing pathway, identified the F-box protein Grr1p as an obligatory factor required for Stp1p/Stp2p processing. Additionally, we have found that a null mutation in the ASI1 (amino acid sensor-independent) gene enables full-length unprocessed Stp1p/Stp2p to enter the nucleus and derepress SPS sensor-dependent genes. The N-terminal domains of Stp1p/Stp2p contain two conserved motifs that are required for proper nuclear exclusion and proteolytic processing. These motifs function in parallel; mutations that abolish processing inhibit signaling, whereas mutations that interfere with cytoplasmic retention result in constitutive derepression of SPS sensor-regulated genes independently of processing. The N-terminal domain of Stp1p is functionally autonomous and transferable to other transcription factors, where its presence confers ASI1-dependent nuclear exclusion and SPS sensor-induced proteolytic processing.

This article has been cited by other articles:

• Boban, M., Ljungdahl, P. O. (2007). Dal81 Enhances Stp1- and Stp2-Dependent Transcription Necessitating Negative Modulation by Inner Nuclear Membrane Protein Asi1 in Saccharomyces cerevisiae. Genetics 176: 2087-2097 [Abstract] [Full Text]  
• Kota, J., Melin-Larsson, M., Ljungdahl, P. O., Forsberg, H. (2007). Ssh4, Rcr2 and Rcr1 Affect Plasma Membrane Transporter Activity in Saccharomyces cerevisiae. Genetics 175: 1681-1694 [Abstract] [Full Text]  
• Zargari, A., Boban, M., Heessen, S., Andreasson, C., Thyberg, J., Ljungdahl, P. O. (2007). Inner Nuclear Membrane Proteins Asi1, Asi2, and Asi3 Function in Concert to Maintain the Latent Properties of Transcription Factors Stp1 and Stp2. J. Biol. Chem. 282: 594-605 [Abstract] [Full Text]  
• Andreasson, C., Heessen, S., Ljungdahl, P. O. (2006). Regulation of transcription factor latency by receptor-activated proteolysis.. Genes Dev. 20: 1563-1568 [Abstract] [Full Text]  
• Boban, M., Zargari, A., Andreasson, C., Heessen, S., Thyberg, J., Ljungdahl, P. O. (2006). Asi1 is an inner nuclear membrane protein that restricts promoter access of two latent transcription factors. J. Cell Biol. 173: 695-707 [Abstract] [Full Text]  
• Poulsen, P., Lo Leggio, L., Kielland-Brandt, M. C. (2006). Mapping of an Internal Protease Cleavage Site in the Ssy5p Component of the Amino Acid Sensor of Saccharomyces cerevisiae and Functional Characterization of the Resulting Pro- and Protease Domains by Gain-of-Function Genetics. Eukaryot Cell 5: 601-608 [Abstract] [Full Text]  
• Cai, H., Kauffman, S., Naider, F., Becker, J. M. (2006). Genomewide Screen Reveals a Wide Regulatory Network for Di/Tripeptide Utilization in Saccharomyces cerevisiae. Genetics 172: 1459-1476 [Abstract] [Full Text]  
• Martinez, P., Ljungdahl, P. O. (2005). Divergence of Stp1 and Stp2 Transcription Factors in Candida albicans Places Virulence Factors Required for Proper Nutrient Acquisition under Amino Acid Control. Mol. Cell. Biol. 25: 9435-9446 [Abstract] [Full Text]  
• Poulsen, P., Wu, B., Gaber, R. F., Kielland-Brandt, M. C. (2005). Constitutive Signal Transduction by Mutant Ssy5p and Ptr3p Components of the SPS Amino Acid Sensor System in Saccharomyces cerevisiae. Eukaryot Cell 4: 1116-1124 [Abstract] [Full Text]