Pichia pastoris 14-3-3 regulates transcriptional activity of the methanol inducible transcription factor Mxr1 by direct interaction

Summary The zinc‐finger transcription factor, Mxr1 activates methanol utilization and peroxisome biogenesis genes in the methylotrophic yeast, Pichia pastoris. Expression of Mxr1‐dependent genes is regulated in response to various carbon sources by an unknown mechanism. We show here that this mechan...

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Bibliographic Details
Published in:	Molecular microbiology Vol. 85; no. 2; pp. 282 - 298
Main Authors:	Parua, Pabitra K., Ryan, Paul M., Trang, Kayla, Young, Elton T.
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-07-2012 Blackwell
Subjects:	Amino Acid Sequence Binding Sites Biological and medical sciences Biosynthesis Eukaryotes Fundamental and applied biological sciences. Psychology Gene expression Gene Expression Regulation, Enzymologic Gene Expression Regulation, Fungal Genetic Complementation Test Methanol Methanol - metabolism Microbiology Miscellaneous Molecular Sequence Data Mycology Phosphorylation Pichia - enzymology Pichia - genetics Pichia - metabolism Pichia pastoris Protein Binding Protein Interaction Mapping Proteins Saccharomyces cerevisiae Saccharomyces cerevisiae - enzymology Saccharomyces cerevisiae - genetics Sequence Homology, Amino Acid Transcription Factors - metabolism Yeast Ascomycota Fungi Regulation(control) Pichia pastoris Transcription factor
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Summary:	Summary The zinc‐finger transcription factor, Mxr1 activates methanol utilization and peroxisome biogenesis genes in the methylotrophic yeast, Pichia pastoris. Expression of Mxr1‐dependent genes is regulated in response to various carbon sources by an unknown mechanism. We show here that this mechanism involves the highly conserved 14‐3‐3 proteins. 14‐3‐3 proteins participate in many biological processes in different eukaryotes. We have characterized a putative 14‐3‐3 binding region at Mxr1 residues 212–225 and mapped the major activation domain of Mxr1 to residues 246–280, and showed that phenylalanine residues in this region are critical for its function. Furthermore, we report that a unique and previously uncharacterized 14‐3‐3 family protein in P. pastoris complements Saccharomyces cerevisiae 14‐3‐3 functions and interacts with Mxr1 through its 14‐3‐3 binding region via phosphorylation of Ser215 in a carbon source‐dependent manner. Indeed, our in vivo results suggest a carbon source‐dependent regulation of expression of Mxr1‐activated genes by 14‐3‐3 in P. pastoris. Interestingly, we observed 14‐3‐3‐independent binding of Mxr1 to the promoters, suggesting a post‐DNA binding function of 14‐3‐3 in regulating transcription. We provide the first molecular explanation of carbon source‐mediated regulation of Mxr1 activity, whose mechanism involves a post‐DNA binding role of 14‐3‐3.
Bibliography:	Supporting info item ArticleID:MMI8112 ark:/67375/WNG-P0CKZQ3G-G istex:7C136D3DBD4D8E0D846E17A0DECFF5F8931EB32B ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0950-382X 1365-2958
DOI:	10.1111/j.1365-2958.2012.08112.x