Identification of ubiquitin-proteasome system components affecting the degradation of the transcription factor Pap1
| Autor: | Kenji Kitamura, Sarela García-Santamarina, Elena Hidalgo, Luis Marte, José Ayté, Susanna Boronat |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Clinical Biochemistry Multidrug resistance SDS-PAGE sodium dodecyl sulfate-polyacrylamide electrophoresis Biochemistry H(2)O(2) tolerance 0302 clinical medicine Ubiquitin Ub ubiquitin lcsh:QH301-705.5 bZIP basic zipper Adenosine Triphosphatases chemistry.chemical_classification lcsh:R5-920 biology Chemistry H2O2 tolerance Ubiquitin ligase Cell biology Amino acid Protein Transport Basic-Leucine Zipper Transcription Factors E3 ubiquitin ligase H2O2 hydrogen peroxide lcsh:Medicine (General) Signal Transduction Research Paper Ubiquitin-Protein Ligases MM minimal medium TCA trichloroacetic acid Ubr1 03 medical and health sciences CHX cycloheximide Caffeine Drug Resistance Multiple Fungal Schizosaccharomyces UPS ubiquitin-proteasome system PQC protein quality control Transcription factor Gene Proteasome Organic Chemistry Hydrogen Peroxide YE yeast extract Pap1 Fusion protein FTC fluorescein 5-thiosemicarbazide 030104 developmental biology lcsh:Biology (General) NLS nuclear localization signal Proteolysis Ubiquitin-Conjugating Enzymes biology.protein Schizosaccharomyces pombe Proteins Degron Gene Deletion 030217 neurology & neurosurgery |
| Zdroj: | Redox Biology, Vol 28, Iss, Pp-(2020) Recercat. Dipósit de la Recerca de Catalunya instname Redox Biology |
| ISSN: | 2213-2317 |
| Popis: | Signaling cascades respond to specific inputs, but also require active interventions to be maintained in their basal/inactive levels in the absence of the activating signal(s). In a screen to search for protein quality control components required for wild-type tolerance to oxidative stress in fission yeast, we have isolated eight gene deletions conferring resistance not only to H2O2 but also to caffeine. We show that dual resistance acquisition is totally or partially dependent on the transcription factor Pap1. Some gene products, such as the ribosomal-ubiquitin fusion protein Ubi1, the E2 conjugating enzyme Ubc2 or the E3 ligase Ubr1, participate in basal ubiquitin labeling of Pap1, and others, such as Rpt4, are non-essential constituents of the proteasome. We demonstrate here that basal nucleo-cytoplasmic shuttling of Pap1, occurring even in the absence of stress, is sufficient for the interaction of the transcription factor with nuclear Ubr1, and we identify a 30 amino acids peptide in Pap1 as the degron for this important E3 ligase. The isolated gene deletions increase only moderately the concentration of the transcription factor, but it is sufficient to enhance basal tolerance to stress, probably by disturbing the inactive stage of this signaling cascade. This work is supported by the Ministerio de Economía y Competitividad (Spain), PLAN E and FEDER (BFU2015-68350-P and PGC2018-093920 to E.H) and by Unidad de Excelencia María de Maeztu (MDM-2014-0370). The Oxidative Stress and Cell Cycle group is also supported by Generalitat de Catalunya (Spain) (2017-SGR-539). E. H. is recipient of an ICREA Academia Award (Generalitat de Catalunya, Spain). |
| Databáze: | OpenAIRE |
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