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Characterization of the transactivation and nuclear localization functions of Pichia pastoris zinc finger transcription factor Mxr1p

Gupta, A and Rao, KK and Sahu, U and Rangarajan, PN (2021) Characterization of the transactivation and nuclear localization functions of Pichia pastoris zinc finger transcription factor Mxr1p. In: Journal of Biological Chemistry, 297 (4).

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Official URL: https://doi.org/10.1016/j.jbc.2021.101247

Abstract

The zinc finger transcription factor Mxr1p regulates the transcription of genes involved in methanol, acetate, and amino acid metabolism of the industrial yeast Pichia pastoris (a.k.a. Komagataella phaffii) by binding to Mxr1p response elements in their promoters. Here, we demonstrate that Mxr1p is a key regulator of ethanol metabolism as well. Using transcriptomic analysis, we identified target genes of Mxr1p that mediate ethanol metabolism, including ALD6-1 encoding an aldehyde dehydrogenase. ALD6-1 is essential for ethanol metabolism, and the ALD6-1 promoter harbors three Mxr1p response elements to which Mxr1p binds in vitro and activates transcription in vivo. We show that a nine-amino acid transactivation domain located between amino acids 365 and 373 of Mxr1p is essential for the transactivation of ALD6-1 to facilitate ethanol metabolism. Mxr1N250, containing the N-terminal 250 amino acids of Mxr1p, localized to the nucleus of cells metabolizing ethanol dependent on basic amino acid residues present between amino acids 75 and 85. While the N-terminal 400 amino acids of Mxr1p are sufficient for the activation of target genes essential for ethanol metabolism, the region between amino acids 401 and 1155 was also required for the regulation of genes essential for methanol metabolism. Finally, we identified several novel genes whose expression is differentially regulated by Mxr1p during methanol metabolism by DNA microarray. This study demonstrates that Mxr1p is a key regulator of ethanol metabolism and provides new insights into the mechanism by which Mxr1p functions as a global regulator of multiple metabolic pathways of P. pastoris. © 2021 The Authors.

Item Type: Journal Article
Publication: Journal of Biological Chemistry
Publisher: American Society for Biochemistry and Molecular Biology Inc.
Additional Information: The copyright for this article belongs to Authors
Keywords: Amino acids; Ethanol; Methanol; Transcription; Transcription factors; Yeast; Zinc, Amino-acids; Key regulators; Localization functions; N-terminals; Nuclear localization; Pichia Pastoris; Response elements; Target genes; Transactivation; Zinc finger transcription factor, Metabolism
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 28 Nov 2021 06:59
Last Modified: 28 Nov 2021 06:59
URI: http://eprints.iisc.ac.in/id/eprint/70427

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