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• W2391743628 abstract "The ubiquitin-proteasome system represents the major pathway of selective intracellular protein degradation in eukaryotes. Misfolded proteins represent an important class of substrates for this pathway, and the failure to destroy misfolded proteins is associated with a number of human diseases. The transcription factor Rpn4 mediates a key proteotoxic stress response whose best known function is to control proteasome abundance by a homeostatic feedback mechanism. Here we identify the uncharacterized zinc finger protein Tmc1 as a dynamically regulated stress-responsive protein. Rpn4 induces TMC1 transcription in response to misfolded proteins. However, this response is counteracted by rapid proteasome-dependent degradation of Tmc1, which serves to normalize Tmc1 protein levels after induction. Precise control of Tmc1 levels is needed in vivo to survive multiple stressors related to proteostasis. Thus, Tmc1 represents a novel effector and substrate of the Rpn4 proteotoxic stress response. The ubiquitin-proteasome system represents the major pathway of selective intracellular protein degradation in eukaryotes. Misfolded proteins represent an important class of substrates for this pathway, and the failure to destroy misfolded proteins is associated with a number of human diseases. The transcription factor Rpn4 mediates a key proteotoxic stress response whose best known function is to control proteasome abundance by a homeostatic feedback mechanism. Here we identify the uncharacterized zinc finger protein Tmc1 as a dynamically regulated stress-responsive protein. Rpn4 induces TMC1 transcription in response to misfolded proteins. However, this response is counteracted by rapid proteasome-dependent degradation of Tmc1, which serves to normalize Tmc1 protein levels after induction. Precise control of Tmc1 levels is needed in vivo to survive multiple stressors related to proteostasis. Thus, Tmc1 represents a novel effector and substrate of the Rpn4 proteotoxic stress response." @default.
• W2391743628 created "2016-06-24" @default.
• W2391743628 creator A5039787720 @default.
• W2391743628 creator A5081556284 @default.
• W2391743628 date "2016-07-01" @default.
• W2391743628 modified "2023-09-30" @default.
• W2391743628 title "Tmc1 Is a Dynamically Regulated Effector of the Rpn4 Proteotoxic Stress Response" @default.
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• W2391743628 doi "https://doi.org/10.1074/jbc.m116.726398" @default.
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