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The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway
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| Zeitschriftentitel: | Journal of Cellular Biochemistry |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , |
| In: | Journal of Cellular Biochemistry, 119, 2018, 2, S. 1979-1991 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
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| Schlagwörter: |
| author_facet |
Ji, Yanxi Cao, Liu Zeng, Lanyi Zhang, Zhen Xiao, Qiaoqiao Guan, Penglin Chen, Shiyou Chen, Yu Wang, Min Guo, Deyin Ji, Yanxi Cao, Liu Zeng, Lanyi Zhang, Zhen Xiao, Qiaoqiao Guan, Penglin Chen, Shiyou Chen, Yu Wang, Min Guo, Deyin |
|---|---|
| author |
Ji, Yanxi Cao, Liu Zeng, Lanyi Zhang, Zhen Xiao, Qiaoqiao Guan, Penglin Chen, Shiyou Chen, Yu Wang, Min Guo, Deyin |
| spellingShingle |
Ji, Yanxi Cao, Liu Zeng, Lanyi Zhang, Zhen Xiao, Qiaoqiao Guan, Penglin Chen, Shiyou Chen, Yu Wang, Min Guo, Deyin Journal of Cellular Biochemistry The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway Cell Biology Molecular Biology Biochemistry |
| author_sort |
ji, yanxi |
| spelling |
Ji, Yanxi Cao, Liu Zeng, Lanyi Zhang, Zhen Xiao, Qiaoqiao Guan, Penglin Chen, Shiyou Chen, Yu Wang, Min Guo, Deyin 0730-2312 1097-4644 Wiley Cell Biology Molecular Biology Biochemistry http://dx.doi.org/10.1002/jcb.26359 <jats:title>Abstract</jats:title><jats:sec><jats:label /><jats:p>Cezanne, a deubiquitinating cysteine protease (DUB) belonging to A20 subgroup of ovarian tumor (OTU) protein superfamily, functions as a negative regulator of NF‐κB to attenuate NF‐κB activation and to restrain pro‐inflammatory transcription in response to TNF receptor (TNFR) signaling. It is the first documented OTU DUB that preferably disassembles Lys11‐linked polyubiquitin chains and has been shown to regulate multiple cellular events including immune signaling, cell survival and tumor progression. Previous studies showed that in response to TNF stimulation, Cezanne is recruited to the activated TNFR complex to suppress the build‐up of polyubiquitinated RIP1 signal by removing Lys63 polyubiquitin from RIP1. However, how is Cezanne recognized and recruited to TNFR complex is not clear yet. In this study, we characterized a ubiquitin‐associated (UBA) domain in the N‐terminal region of Cezanne and proved its activity to bind Lys63 polyubiquitin chain. By constructing a series of truncated and site‐specific point mutants, we further localized the crucial binding sites for Lys63 polyubiquitin chains at Leu9 and Ser10 sites of Cezanne UBA domain. Mutation at these sites disrupted the recruitment of Cezanne to activated TNFR complex and dramatically reduced the inhibition of NF‐κB activation by Cezanne. Our study demonstrated that the N‐terminal UBA domain is crucial for the function of Cezanne during NF‐κB activation. Cezanne is recognized and recruited into activated TNFR complex by specifically binding to polyubiquitinated signaling proteins after TNF stimulation through its N‐terminal polyubiquitin binding site. This study sheds light on the molecular mechanism of negative regulation of NF‐κB activation by Cezanne.</jats:p></jats:sec> The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway Journal of Cellular Biochemistry |
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10.1002/jcb.26359 |
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Online |
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Biologie Chemie und Pharmazie |
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Wiley, 2018 |
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Wiley, 2018 |
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2018 |
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Journal of Cellular Biochemistry |
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| title |
The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway |
| title_unstemmed |
The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway |
| title_full |
The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway |
| title_fullStr |
The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway |
| title_full_unstemmed |
The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway |
| title_short |
The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway |
| title_sort |
the n‐terminal ubiquitin‐associated domain of cezanne is crucial for its function to suppress nf‐κb pathway |
| topic |
Cell Biology Molecular Biology Biochemistry |
| url |
http://dx.doi.org/10.1002/jcb.26359 |
| publishDate |
2018 |
| physical |
1979-1991 |
| description |
<jats:title>Abstract</jats:title><jats:sec><jats:label /><jats:p>Cezanne, a deubiquitinating cysteine protease (DUB) belonging to A20 subgroup of ovarian tumor (OTU) protein superfamily, functions as a negative regulator of NF‐κB to attenuate NF‐κB activation and to restrain pro‐inflammatory transcription in response to TNF receptor (TNFR) signaling. It is the first documented OTU DUB that preferably disassembles Lys11‐linked polyubiquitin chains and has been shown to regulate multiple cellular events including immune signaling, cell survival and tumor progression. Previous studies showed that in response to TNF stimulation, Cezanne is recruited to the activated TNFR complex to suppress the build‐up of polyubiquitinated RIP1 signal by removing Lys63 polyubiquitin from RIP1. However, how is Cezanne recognized and recruited to TNFR complex is not clear yet. In this study, we characterized a ubiquitin‐associated (UBA) domain in the N‐terminal region of Cezanne and proved its activity to bind Lys63 polyubiquitin chain. By constructing a series of truncated and site‐specific point mutants, we further localized the crucial binding sites for Lys63 polyubiquitin chains at Leu9 and Ser10 sites of Cezanne UBA domain. Mutation at these sites disrupted the recruitment of Cezanne to activated TNFR complex and dramatically reduced the inhibition of NF‐κB activation by Cezanne. Our study demonstrated that the N‐terminal UBA domain is crucial for the function of Cezanne during NF‐κB activation. Cezanne is recognized and recruited into activated TNFR complex by specifically binding to polyubiquitinated signaling proteins after TNF stimulation through its N‐terminal polyubiquitin binding site. This study sheds light on the molecular mechanism of negative regulation of NF‐κB activation by Cezanne.</jats:p></jats:sec> |
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| author | Ji, Yanxi, Cao, Liu, Zeng, Lanyi, Zhang, Zhen, Xiao, Qiaoqiao, Guan, Penglin, Chen, Shiyou, Chen, Yu, Wang, Min, Guo, Deyin |
| author_facet | Ji, Yanxi, Cao, Liu, Zeng, Lanyi, Zhang, Zhen, Xiao, Qiaoqiao, Guan, Penglin, Chen, Shiyou, Chen, Yu, Wang, Min, Guo, Deyin, Ji, Yanxi, Cao, Liu, Zeng, Lanyi, Zhang, Zhen, Xiao, Qiaoqiao, Guan, Penglin, Chen, Shiyou, Chen, Yu, Wang, Min, Guo, Deyin |
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| container_title | Journal of Cellular Biochemistry |
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| description | <jats:title>Abstract</jats:title><jats:sec><jats:label /><jats:p>Cezanne, a deubiquitinating cysteine protease (DUB) belonging to A20 subgroup of ovarian tumor (OTU) protein superfamily, functions as a negative regulator of NF‐κB to attenuate NF‐κB activation and to restrain pro‐inflammatory transcription in response to TNF receptor (TNFR) signaling. It is the first documented OTU DUB that preferably disassembles Lys11‐linked polyubiquitin chains and has been shown to regulate multiple cellular events including immune signaling, cell survival and tumor progression. Previous studies showed that in response to TNF stimulation, Cezanne is recruited to the activated TNFR complex to suppress the build‐up of polyubiquitinated RIP1 signal by removing Lys63 polyubiquitin from RIP1. However, how is Cezanne recognized and recruited to TNFR complex is not clear yet. In this study, we characterized a ubiquitin‐associated (UBA) domain in the N‐terminal region of Cezanne and proved its activity to bind Lys63 polyubiquitin chain. By constructing a series of truncated and site‐specific point mutants, we further localized the crucial binding sites for Lys63 polyubiquitin chains at Leu9 and Ser10 sites of Cezanne UBA domain. Mutation at these sites disrupted the recruitment of Cezanne to activated TNFR complex and dramatically reduced the inhibition of NF‐κB activation by Cezanne. Our study demonstrated that the N‐terminal UBA domain is crucial for the function of Cezanne during NF‐κB activation. Cezanne is recognized and recruited into activated TNFR complex by specifically binding to polyubiquitinated signaling proteins after TNF stimulation through its N‐terminal polyubiquitin binding site. This study sheds light on the molecular mechanism of negative regulation of NF‐κB activation by Cezanne.</jats:p></jats:sec> |
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| imprint | Wiley, 2018 |
| imprint_str_mv | Wiley, 2018 |
| institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-D161 |
| issn | 0730-2312, 1097-4644 |
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| series | Journal of Cellular Biochemistry |
| source_id | 49 |
| spelling | Ji, Yanxi Cao, Liu Zeng, Lanyi Zhang, Zhen Xiao, Qiaoqiao Guan, Penglin Chen, Shiyou Chen, Yu Wang, Min Guo, Deyin 0730-2312 1097-4644 Wiley Cell Biology Molecular Biology Biochemistry http://dx.doi.org/10.1002/jcb.26359 <jats:title>Abstract</jats:title><jats:sec><jats:label /><jats:p>Cezanne, a deubiquitinating cysteine protease (DUB) belonging to A20 subgroup of ovarian tumor (OTU) protein superfamily, functions as a negative regulator of NF‐κB to attenuate NF‐κB activation and to restrain pro‐inflammatory transcription in response to TNF receptor (TNFR) signaling. It is the first documented OTU DUB that preferably disassembles Lys11‐linked polyubiquitin chains and has been shown to regulate multiple cellular events including immune signaling, cell survival and tumor progression. Previous studies showed that in response to TNF stimulation, Cezanne is recruited to the activated TNFR complex to suppress the build‐up of polyubiquitinated RIP1 signal by removing Lys63 polyubiquitin from RIP1. However, how is Cezanne recognized and recruited to TNFR complex is not clear yet. In this study, we characterized a ubiquitin‐associated (UBA) domain in the N‐terminal region of Cezanne and proved its activity to bind Lys63 polyubiquitin chain. By constructing a series of truncated and site‐specific point mutants, we further localized the crucial binding sites for Lys63 polyubiquitin chains at Leu9 and Ser10 sites of Cezanne UBA domain. Mutation at these sites disrupted the recruitment of Cezanne to activated TNFR complex and dramatically reduced the inhibition of NF‐κB activation by Cezanne. Our study demonstrated that the N‐terminal UBA domain is crucial for the function of Cezanne during NF‐κB activation. Cezanne is recognized and recruited into activated TNFR complex by specifically binding to polyubiquitinated signaling proteins after TNF stimulation through its N‐terminal polyubiquitin binding site. This study sheds light on the molecular mechanism of negative regulation of NF‐κB activation by Cezanne.</jats:p></jats:sec> The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway Journal of Cellular Biochemistry |
| spellingShingle | Ji, Yanxi, Cao, Liu, Zeng, Lanyi, Zhang, Zhen, Xiao, Qiaoqiao, Guan, Penglin, Chen, Shiyou, Chen, Yu, Wang, Min, Guo, Deyin, Journal of Cellular Biochemistry, The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway, Cell Biology, Molecular Biology, Biochemistry |
| title | The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway |
| title_full | The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway |
| title_fullStr | The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway |
| title_full_unstemmed | The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway |
| title_short | The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway |
| title_sort | the n‐terminal ubiquitin‐associated domain of cezanne is crucial for its function to suppress nf‐κb pathway |
| title_unstemmed | The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway |
| topic | Cell Biology, Molecular Biology, Biochemistry |
| url | http://dx.doi.org/10.1002/jcb.26359 |