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Alan D. D'andrea - One of the best experts on this subject based on the ideXlab platform.
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WDR20 Regulates Activity of the USP12·UAF1 Deubiquitinating Enzyme Complex
Journal of Biological Chemistry, 2010Co-Authors: Kailin Yang, Wilhelm Haas, Martin A. Cohn, Stephen P. Gygi, Alan D. D'andreaAbstract:The UAF1 (Usp1-associated factor 1) protein binds and stimulates three Deubiquitinating Enzymes: USP1, USP12, and USP46. Although the USP1·UAF1 complex is required for regulation of the Fanconi anemia (FA) DNA repair pathway, less is known about the USP12·UAF1 and the USP46·UAF1 complexes. To understand further the nature of the USP12 and USP46 complexes, we attempted to identify proteins that interact with the USP12 and USP46 Deubiquitinating Enzyme complexes. We identified WDR20, a WD40-repeat containing protein, as a common binding partner of UAF1, USP12, and USP46. Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1. Furthermore, we demonstrate the purification of a ternary USP12·UAF1·WDR20 complex. Interestingly, and consistent with the binding assays, WDR20 stimulated the enzymatic activity of USP12·UAF1, but not of USP1·UAF1. Consistent with our previous report that USP12 and USP46 do not regulate the FA pathway, small interference RNA-mediated depletion of WDR20 protein did not affect the FA pathway or DNA damage responses. We provide a model in which WDR20 serves as a stimulatory subunit for preserving and regulating the activity of the subset of the UAF1·USP complexes.
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UAF1 is a subunit of multiple Deubiquitinating Enzyme complexes.
Journal of Biological Chemistry, 2008Co-Authors: Martin A. Cohn, Wilhelm Haas, Stephen P. Gygi, Alan D. D'andreaAbstract:A balance between ubiquitination and deubiquitination regulates numerous cellular processes and pathways, and specific Deubiquitinating Enzymes often play the decisive role of controlling this balance. We recently reported that the USP1 Deubiquitinating Enzyme, which regulates the Fanconi anemia pathway by Deubiquitinating the central player of the pathway, FANCD2, is activated by the WD40-repeat containing UAF1 protein through formation of a stable USP1/UAF1 protein complex. Here we present the isolation of two novel multisubunit Deubiquitinating Enzyme complexes containing USP12 and USP46, respectively. Both complexes contain the UAF1 protein as a bona fide subunit. Interestingly, UAF1 regulates the enzymatic activity of both Enzyme complexes, suggesting that this activator protein may regulate a subclass of human Deubiquitinating Enzymes. We postulate that additional WD40-containing proteins may also form complexes with other human Deubiquitinating Enzymes and thereby regulate their activity and substrate specificity.
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DUB-1, a Deubiquitinating Enzyme with growth-suppressing activity.
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Yuan Zhu, Mark Hochstrasser, Feroz R. Papa, Martin Carroll, Alan D. D'andreaAbstract:Abstract Cytokines regulate cell growth by inducing the expression of specific target genes. Using the differential display method, we have cloned a cytokine-inducible immediate early gene, DUB-1 (for Deubiquitinating Enzyme). DUB-1 is related to members of the UBP superfamily of Deubiquitinating Enzymes, which includes the oncoprotein Tre-2. A glutathione S-transferase-DUB-1 fusion protein cleaved ubiquitin from a ubiquitin-beta-galactosidase protein. When a conserved cysteine residue of DUB-1, required for ubiquitin-specific thiol protease activity, was mutated to serine (C60S), Deubiquitinating activity was abolished. Continuous expression of DUB-1 from a steroid-inducible promoter induced growth arrest in the G1 phase of the cell cycle. Cells arrested by DUB-1 expression remained viable and resumed proliferation upon steroid withdrawal. Our results suggest that DUB-1 regulates cellular growth by modulating either the ubiquitin-dependent proteolysis or the ubiquitination state of an unknown growth regulatory factor(s).
Martin A. Cohn - One of the best experts on this subject based on the ideXlab platform.
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wdr20 regulates activity of the usp12 uaf1 Deubiquitinating Enzyme complex
Journal of Biological Chemistry, 2010Co-Authors: Younghoon Kee, Wilhelm Haas, Martin A. Cohn, Kailin Yang, Stephen P. Gygi, Alan D DandreaAbstract:The UAF1 (Usp1-associated factor 1) protein binds and stimulates three Deubiquitinating Enzymes: USP1, USP12, and USP46. Although the USP1·UAF1 complex is required for regulation of the Fanconi anemia (FA) DNA repair pathway, less is known about the USP12·UAF1 and the USP46·UAF1 complexes. To understand further the nature of the USP12 and USP46 complexes, we attempted to identify proteins that interact with the USP12 and USP46 Deubiquitinating Enzyme complexes. We identified WDR20, a WD40-repeat containing protein, as a common binding partner of UAF1, USP12, and USP46. Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1. Furthermore, we demonstrate the purification of a ternary USP12·UAF1·WDR20 complex. Interestingly, and consistent with the binding assays, WDR20 stimulated the enzymatic activity of USP12·UAF1, but not of USP1·UAF1. Consistent with our previous report that USP12 and USP46 do not regulate the FA pathway, small interference RNA-mediated depletion of WDR20 protein did not affect the FA pathway or DNA damage responses. We provide a model in which WDR20 serves as a stimulatory subunit for preserving and regulating the activity of the subset of the UAF1·USP complexes.
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WDR20 Regulates Activity of the USP12·UAF1 Deubiquitinating Enzyme Complex
Journal of Biological Chemistry, 2010Co-Authors: Kailin Yang, Wilhelm Haas, Martin A. Cohn, Stephen P. Gygi, Alan D. D'andreaAbstract:The UAF1 (Usp1-associated factor 1) protein binds and stimulates three Deubiquitinating Enzymes: USP1, USP12, and USP46. Although the USP1·UAF1 complex is required for regulation of the Fanconi anemia (FA) DNA repair pathway, less is known about the USP12·UAF1 and the USP46·UAF1 complexes. To understand further the nature of the USP12 and USP46 complexes, we attempted to identify proteins that interact with the USP12 and USP46 Deubiquitinating Enzyme complexes. We identified WDR20, a WD40-repeat containing protein, as a common binding partner of UAF1, USP12, and USP46. Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1. Furthermore, we demonstrate the purification of a ternary USP12·UAF1·WDR20 complex. Interestingly, and consistent with the binding assays, WDR20 stimulated the enzymatic activity of USP12·UAF1, but not of USP1·UAF1. Consistent with our previous report that USP12 and USP46 do not regulate the FA pathway, small interference RNA-mediated depletion of WDR20 protein did not affect the FA pathway or DNA damage responses. We provide a model in which WDR20 serves as a stimulatory subunit for preserving and regulating the activity of the subset of the UAF1·USP complexes.
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UAF1 is a subunit of multiple Deubiquitinating Enzyme complexes.
Journal of Biological Chemistry, 2008Co-Authors: Martin A. Cohn, Wilhelm Haas, Stephen P. Gygi, Alan D. D'andreaAbstract:A balance between ubiquitination and deubiquitination regulates numerous cellular processes and pathways, and specific Deubiquitinating Enzymes often play the decisive role of controlling this balance. We recently reported that the USP1 Deubiquitinating Enzyme, which regulates the Fanconi anemia pathway by Deubiquitinating the central player of the pathway, FANCD2, is activated by the WD40-repeat containing UAF1 protein through formation of a stable USP1/UAF1 protein complex. Here we present the isolation of two novel multisubunit Deubiquitinating Enzyme complexes containing USP12 and USP46, respectively. Both complexes contain the UAF1 protein as a bona fide subunit. Interestingly, UAF1 regulates the enzymatic activity of both Enzyme complexes, suggesting that this activator protein may regulate a subclass of human Deubiquitinating Enzymes. We postulate that additional WD40-containing proteins may also form complexes with other human Deubiquitinating Enzymes and thereby regulate their activity and substrate specificity.
Stephen P. Gygi - One of the best experts on this subject based on the ideXlab platform.
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wdr20 regulates activity of the usp12 uaf1 Deubiquitinating Enzyme complex
Journal of Biological Chemistry, 2010Co-Authors: Younghoon Kee, Wilhelm Haas, Martin A. Cohn, Kailin Yang, Stephen P. Gygi, Alan D DandreaAbstract:The UAF1 (Usp1-associated factor 1) protein binds and stimulates three Deubiquitinating Enzymes: USP1, USP12, and USP46. Although the USP1·UAF1 complex is required for regulation of the Fanconi anemia (FA) DNA repair pathway, less is known about the USP12·UAF1 and the USP46·UAF1 complexes. To understand further the nature of the USP12 and USP46 complexes, we attempted to identify proteins that interact with the USP12 and USP46 Deubiquitinating Enzyme complexes. We identified WDR20, a WD40-repeat containing protein, as a common binding partner of UAF1, USP12, and USP46. Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1. Furthermore, we demonstrate the purification of a ternary USP12·UAF1·WDR20 complex. Interestingly, and consistent with the binding assays, WDR20 stimulated the enzymatic activity of USP12·UAF1, but not of USP1·UAF1. Consistent with our previous report that USP12 and USP46 do not regulate the FA pathway, small interference RNA-mediated depletion of WDR20 protein did not affect the FA pathway or DNA damage responses. We provide a model in which WDR20 serves as a stimulatory subunit for preserving and regulating the activity of the subset of the UAF1·USP complexes.
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WDR20 Regulates Activity of the USP12·UAF1 Deubiquitinating Enzyme Complex
Journal of Biological Chemistry, 2010Co-Authors: Kailin Yang, Wilhelm Haas, Martin A. Cohn, Stephen P. Gygi, Alan D. D'andreaAbstract:The UAF1 (Usp1-associated factor 1) protein binds and stimulates three Deubiquitinating Enzymes: USP1, USP12, and USP46. Although the USP1·UAF1 complex is required for regulation of the Fanconi anemia (FA) DNA repair pathway, less is known about the USP12·UAF1 and the USP46·UAF1 complexes. To understand further the nature of the USP12 and USP46 complexes, we attempted to identify proteins that interact with the USP12 and USP46 Deubiquitinating Enzyme complexes. We identified WDR20, a WD40-repeat containing protein, as a common binding partner of UAF1, USP12, and USP46. Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1. Furthermore, we demonstrate the purification of a ternary USP12·UAF1·WDR20 complex. Interestingly, and consistent with the binding assays, WDR20 stimulated the enzymatic activity of USP12·UAF1, but not of USP1·UAF1. Consistent with our previous report that USP12 and USP46 do not regulate the FA pathway, small interference RNA-mediated depletion of WDR20 protein did not affect the FA pathway or DNA damage responses. We provide a model in which WDR20 serves as a stimulatory subunit for preserving and regulating the activity of the subset of the UAF1·USP complexes.
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UAF1 is a subunit of multiple Deubiquitinating Enzyme complexes.
Journal of Biological Chemistry, 2008Co-Authors: Martin A. Cohn, Wilhelm Haas, Stephen P. Gygi, Alan D. D'andreaAbstract:A balance between ubiquitination and deubiquitination regulates numerous cellular processes and pathways, and specific Deubiquitinating Enzymes often play the decisive role of controlling this balance. We recently reported that the USP1 Deubiquitinating Enzyme, which regulates the Fanconi anemia pathway by Deubiquitinating the central player of the pathway, FANCD2, is activated by the WD40-repeat containing UAF1 protein through formation of a stable USP1/UAF1 protein complex. Here we present the isolation of two novel multisubunit Deubiquitinating Enzyme complexes containing USP12 and USP46, respectively. Both complexes contain the UAF1 protein as a bona fide subunit. Interestingly, UAF1 regulates the enzymatic activity of both Enzyme complexes, suggesting that this activator protein may regulate a subclass of human Deubiquitinating Enzymes. We postulate that additional WD40-containing proteins may also form complexes with other human Deubiquitinating Enzymes and thereby regulate their activity and substrate specificity.
Wilhelm Haas - One of the best experts on this subject based on the ideXlab platform.
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wdr20 regulates activity of the usp12 uaf1 Deubiquitinating Enzyme complex
Journal of Biological Chemistry, 2010Co-Authors: Younghoon Kee, Wilhelm Haas, Martin A. Cohn, Kailin Yang, Stephen P. Gygi, Alan D DandreaAbstract:The UAF1 (Usp1-associated factor 1) protein binds and stimulates three Deubiquitinating Enzymes: USP1, USP12, and USP46. Although the USP1·UAF1 complex is required for regulation of the Fanconi anemia (FA) DNA repair pathway, less is known about the USP12·UAF1 and the USP46·UAF1 complexes. To understand further the nature of the USP12 and USP46 complexes, we attempted to identify proteins that interact with the USP12 and USP46 Deubiquitinating Enzyme complexes. We identified WDR20, a WD40-repeat containing protein, as a common binding partner of UAF1, USP12, and USP46. Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1. Furthermore, we demonstrate the purification of a ternary USP12·UAF1·WDR20 complex. Interestingly, and consistent with the binding assays, WDR20 stimulated the enzymatic activity of USP12·UAF1, but not of USP1·UAF1. Consistent with our previous report that USP12 and USP46 do not regulate the FA pathway, small interference RNA-mediated depletion of WDR20 protein did not affect the FA pathway or DNA damage responses. We provide a model in which WDR20 serves as a stimulatory subunit for preserving and regulating the activity of the subset of the UAF1·USP complexes.
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WDR20 Regulates Activity of the USP12·UAF1 Deubiquitinating Enzyme Complex
Journal of Biological Chemistry, 2010Co-Authors: Kailin Yang, Wilhelm Haas, Martin A. Cohn, Stephen P. Gygi, Alan D. D'andreaAbstract:The UAF1 (Usp1-associated factor 1) protein binds and stimulates three Deubiquitinating Enzymes: USP1, USP12, and USP46. Although the USP1·UAF1 complex is required for regulation of the Fanconi anemia (FA) DNA repair pathway, less is known about the USP12·UAF1 and the USP46·UAF1 complexes. To understand further the nature of the USP12 and USP46 complexes, we attempted to identify proteins that interact with the USP12 and USP46 Deubiquitinating Enzyme complexes. We identified WDR20, a WD40-repeat containing protein, as a common binding partner of UAF1, USP12, and USP46. Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1. Furthermore, we demonstrate the purification of a ternary USP12·UAF1·WDR20 complex. Interestingly, and consistent with the binding assays, WDR20 stimulated the enzymatic activity of USP12·UAF1, but not of USP1·UAF1. Consistent with our previous report that USP12 and USP46 do not regulate the FA pathway, small interference RNA-mediated depletion of WDR20 protein did not affect the FA pathway or DNA damage responses. We provide a model in which WDR20 serves as a stimulatory subunit for preserving and regulating the activity of the subset of the UAF1·USP complexes.
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UAF1 is a subunit of multiple Deubiquitinating Enzyme complexes.
Journal of Biological Chemistry, 2008Co-Authors: Martin A. Cohn, Wilhelm Haas, Stephen P. Gygi, Alan D. D'andreaAbstract:A balance between ubiquitination and deubiquitination regulates numerous cellular processes and pathways, and specific Deubiquitinating Enzymes often play the decisive role of controlling this balance. We recently reported that the USP1 Deubiquitinating Enzyme, which regulates the Fanconi anemia pathway by Deubiquitinating the central player of the pathway, FANCD2, is activated by the WD40-repeat containing UAF1 protein through formation of a stable USP1/UAF1 protein complex. Here we present the isolation of two novel multisubunit Deubiquitinating Enzyme complexes containing USP12 and USP46, respectively. Both complexes contain the UAF1 protein as a bona fide subunit. Interestingly, UAF1 regulates the enzymatic activity of both Enzyme complexes, suggesting that this activator protein may regulate a subclass of human Deubiquitinating Enzymes. We postulate that additional WD40-containing proteins may also form complexes with other human Deubiquitinating Enzymes and thereby regulate their activity and substrate specificity.
Alan D Dandrea - One of the best experts on this subject based on the ideXlab platform.
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wdr20 regulates activity of the usp12 uaf1 Deubiquitinating Enzyme complex
Journal of Biological Chemistry, 2010Co-Authors: Younghoon Kee, Wilhelm Haas, Martin A. Cohn, Kailin Yang, Stephen P. Gygi, Alan D DandreaAbstract:The UAF1 (Usp1-associated factor 1) protein binds and stimulates three Deubiquitinating Enzymes: USP1, USP12, and USP46. Although the USP1·UAF1 complex is required for regulation of the Fanconi anemia (FA) DNA repair pathway, less is known about the USP12·UAF1 and the USP46·UAF1 complexes. To understand further the nature of the USP12 and USP46 complexes, we attempted to identify proteins that interact with the USP12 and USP46 Deubiquitinating Enzyme complexes. We identified WDR20, a WD40-repeat containing protein, as a common binding partner of UAF1, USP12, and USP46. Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1. Furthermore, we demonstrate the purification of a ternary USP12·UAF1·WDR20 complex. Interestingly, and consistent with the binding assays, WDR20 stimulated the enzymatic activity of USP12·UAF1, but not of USP1·UAF1. Consistent with our previous report that USP12 and USP46 do not regulate the FA pathway, small interference RNA-mediated depletion of WDR20 protein did not affect the FA pathway or DNA damage responses. We provide a model in which WDR20 serves as a stimulatory subunit for preserving and regulating the activity of the subset of the UAF1·USP complexes.
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the Deubiquitinating Enzyme usp1 regulates the fanconi anemia pathway
Molecular Cell, 2005Co-Authors: Sebastian M B Nijman, Tony T. Huang, Thijn R Brummelkamp, Ron M. Kerkhoven, Alan D Dandrea, Annette M G Dirac, Rene BernardsAbstract:Protein ubiquitination and deubiquitination are dynamic processes implicated in the regulation of numerous cellular pathways. Monoubiquitination of the Fanconi anemia (FA) protein FANCD2 appears to be critical in the repair of DNA damage because many of the proteins that are mutated in FA are required for FANCD2 ubiquitination. By screening a gene family RNAi library, we identify the Deubiquitinating Enzyme USP1 as a novel component of the Fanconi anemia pathway. Inhibition of USP1 leads to hyperaccumulation of monoubiquitinated FANCD2. Furthermore, USP1 physically associates with FANCD2, and the proteins colocalize in chromatin after DNA damage. Finally, analysis of crosslinker-induced chromosomal aberrations in USP1 knockdown cells suggests a role in DNA repair. We propose that USP1 deubiquitinates FANCD2 when cells exit S phase or recommence cycling after a DNA damage insult and may play a critical role in the FA pathway by recycling FANCD2.