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A double role of the Gal80 N terminus in activation of transcription by Gal4p
The yeast galactose switch operated by the Gal4p–Gal80p–Gal3p regulatory module is a textbook model of transcription regulation in eukaryotes. The Gal80 protein inhibits Gal4p-mediated transcription activation by binding to the transcription activation domain. In Saccharomyces cerevisiae, inhibition...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556753/ https://www.ncbi.nlm.nih.gov/pubmed/33037058 http://dx.doi.org/10.26508/lsa.202000665 |
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author | Reinhardt-Tews, Annekathrin Krutyhołowa, Rościsław Günzel, Christian Roehl, Constance Glatt, Sebastian Breunig, Karin D |
author_facet | Reinhardt-Tews, Annekathrin Krutyhołowa, Rościsław Günzel, Christian Roehl, Constance Glatt, Sebastian Breunig, Karin D |
author_sort | Reinhardt-Tews, Annekathrin |
collection | PubMed |
description | The yeast galactose switch operated by the Gal4p–Gal80p–Gal3p regulatory module is a textbook model of transcription regulation in eukaryotes. The Gal80 protein inhibits Gal4p-mediated transcription activation by binding to the transcription activation domain. In Saccharomyces cerevisiae, inhibition is relieved by formation of an alternative Gal80–Gal3 complex. In yeasts lacking a Gal3p ortholog, such as Kluyveromyces lactis, the Gal1 protein (KlGal1p) combines regulatory and enzymatic activity. The data presented here reveal a yet unknown role of the KlGal80 N terminus in the mechanism of Gal4p activation. The N terminus contains an NLS, which is responsible for nuclear accumulation of KlGal80p and KlGal1p and for KlGal80p-mediated galactokinase inhibition. Herein, we present a model where the N terminus of KlGal80p reaches the catalytic center of KlGal1p causing enzyme inhibition in the nucleus and stabilization of the KlGal1–KlGal80p complex. We corroborate this model by genetic analyses and structural modelling and provide a rationale for the divergent evolution of the mechanism activating Gal4p. |
format | Online Article Text |
id | pubmed-7556753 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-75567532020-10-27 A double role of the Gal80 N terminus in activation of transcription by Gal4p Reinhardt-Tews, Annekathrin Krutyhołowa, Rościsław Günzel, Christian Roehl, Constance Glatt, Sebastian Breunig, Karin D Life Sci Alliance Research Articles The yeast galactose switch operated by the Gal4p–Gal80p–Gal3p regulatory module is a textbook model of transcription regulation in eukaryotes. The Gal80 protein inhibits Gal4p-mediated transcription activation by binding to the transcription activation domain. In Saccharomyces cerevisiae, inhibition is relieved by formation of an alternative Gal80–Gal3 complex. In yeasts lacking a Gal3p ortholog, such as Kluyveromyces lactis, the Gal1 protein (KlGal1p) combines regulatory and enzymatic activity. The data presented here reveal a yet unknown role of the KlGal80 N terminus in the mechanism of Gal4p activation. The N terminus contains an NLS, which is responsible for nuclear accumulation of KlGal80p and KlGal1p and for KlGal80p-mediated galactokinase inhibition. Herein, we present a model where the N terminus of KlGal80p reaches the catalytic center of KlGal1p causing enzyme inhibition in the nucleus and stabilization of the KlGal1–KlGal80p complex. We corroborate this model by genetic analyses and structural modelling and provide a rationale for the divergent evolution of the mechanism activating Gal4p. Life Science Alliance LLC 2020-10-09 /pmc/articles/PMC7556753/ /pubmed/33037058 http://dx.doi.org/10.26508/lsa.202000665 Text en © 2020 Reinhardt-Tews et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Reinhardt-Tews, Annekathrin Krutyhołowa, Rościsław Günzel, Christian Roehl, Constance Glatt, Sebastian Breunig, Karin D A double role of the Gal80 N terminus in activation of transcription by Gal4p |
title | A double role of the Gal80 N terminus in activation of transcription by Gal4p |
title_full | A double role of the Gal80 N terminus in activation of transcription by Gal4p |
title_fullStr | A double role of the Gal80 N terminus in activation of transcription by Gal4p |
title_full_unstemmed | A double role of the Gal80 N terminus in activation of transcription by Gal4p |
title_short | A double role of the Gal80 N terminus in activation of transcription by Gal4p |
title_sort | double role of the gal80 n terminus in activation of transcription by gal4p |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556753/ https://www.ncbi.nlm.nih.gov/pubmed/33037058 http://dx.doi.org/10.26508/lsa.202000665 |
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