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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 HO 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 article was published in the following journal.
Name: Redox biology
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Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).
An adaptor protein characterized by an N-terminal BTB-POZ DOMAIN and six KELCH REPEATS that functions as a substrate for the E3 UBIQUITIN LIGASE complex. It negatively-regulates NF-E2-RELATED FACTOR 2 by targeting it for ubiquitination and degradation by the PROTEASOME. It also represses genes regulated by ANTIOXIDANT RESPONSE ELEMENTS.
A ubiquitin-like protein that functions in CELL CYCLE regulation and embryogenesis. It is attached covalently to its substrates following activation by the UBIQUITIN-ACTIVATING ENZYME E1-UBA3 enzyme complex. NEDD8 attaches to CULLINS, activating their E3 UBIQUITIN LIGASE activity, to promote polyubiquitination and degradation of CYCLINS and regulatory proteins
A degradation process whereby incorrectly folded proteins are selectively transported out of the ENDOPLASMIC RETICULUM and into the CYTOSOL. The misfolded proteins are subsequently ubiquitinated and degraded by the PROTEASOME.
E3 ubiquitin ligases that consist of four WW DOMAINS. They accept UBIQUITIN from E2 UBIQUITIN-CONJUGATING ENZYME as a thioester via their C-terminal HECT domains and transfer it specifically to the 63rd LYSINE residue (Lys-63) of target proteins. NEDD4 targets include many proteins and receptors with important functions for cell growth and homeostasis such as VEGFR-2; FGFR1 TYROSINE KINASE; and ERBB-4 RECEPTOR. They play a critical role in the internalization of these receptors, their degradation by LYSOSOMES, and also function as part of the ESCRT complex in VIRUS RELEASE.
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