Casitas B-Lineage Lymphoma RING Domain Inhibitors Protect Mice against High-Fat Diet-Induced Obesity and Insulin Resistance.
The casitas b-lineage lymphoma (c-Cbl) is an important adaptor protein with an intrinsic E3 ubiquitin ligase activity that interacts with E2 proteins such as UbCH7. c-Cbl plays a vital role in regulating receptor tyrosine kinase signaling. c-Cbl involves in whole-body energy homeostasis, which makes...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4546618?pdf=render |
| _version_ | 1818549874415632384 |
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| author | Min Wu Lin Sun Ziyan Yuan Pessetto Zhihe Zang Xingliang Xie Ling Zhong Qing Su Wang Zan Xiurong Gao Yan Zhao Yiyi Sun |
| author_facet | Min Wu Lin Sun Ziyan Yuan Pessetto Zhihe Zang Xingliang Xie Ling Zhong Qing Su Wang Zan Xiurong Gao Yan Zhao Yiyi Sun |
| author_sort | Min Wu |
| collection | DOAJ |
| description | The casitas b-lineage lymphoma (c-Cbl) is an important adaptor protein with an intrinsic E3 ubiquitin ligase activity that interacts with E2 proteins such as UbCH7. c-Cbl plays a vital role in regulating receptor tyrosine kinase signaling. c-Cbl involves in whole-body energy homeostasis, which makes it a potential target for the treatment of type 2 diabetes and obesity. In the present study, we have designed two parental peptides and 55 modified peptides based on the structure of UbCH7 loop L1 and L2. Thirteen of the modified peptides showed increased inhibitory activity in a fluorescence polarization-based assay. In the in vivo proof of study principle, mice treated with peptides 10, 34, 49 and 51 were protected against high-fat diet-induced obesity and insulin resistant. These inhibitors may potentially lead to new therapeutic alternatives for obesity and type 2 diabetes. |
| first_indexed | 2024-12-12T08:38:57Z |
| format | Article |
| id | doaj.art-ab19abbddf7c48eebe29ee9ae3c53735 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T08:38:57Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ab19abbddf7c48eebe29ee9ae3c537352022-12-22T00:30:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013591610.1371/journal.pone.0135916Casitas B-Lineage Lymphoma RING Domain Inhibitors Protect Mice against High-Fat Diet-Induced Obesity and Insulin Resistance.Min WuLin SunZiyan Yuan PessettoZhihe ZangXingliang XieLing ZhongQing SuWang ZanXiurong GaoYan ZhaoYiyi SunThe casitas b-lineage lymphoma (c-Cbl) is an important adaptor protein with an intrinsic E3 ubiquitin ligase activity that interacts with E2 proteins such as UbCH7. c-Cbl plays a vital role in regulating receptor tyrosine kinase signaling. c-Cbl involves in whole-body energy homeostasis, which makes it a potential target for the treatment of type 2 diabetes and obesity. In the present study, we have designed two parental peptides and 55 modified peptides based on the structure of UbCH7 loop L1 and L2. Thirteen of the modified peptides showed increased inhibitory activity in a fluorescence polarization-based assay. In the in vivo proof of study principle, mice treated with peptides 10, 34, 49 and 51 were protected against high-fat diet-induced obesity and insulin resistant. These inhibitors may potentially lead to new therapeutic alternatives for obesity and type 2 diabetes.http://europepmc.org/articles/PMC4546618?pdf=render |
| spellingShingle | Min Wu Lin Sun Ziyan Yuan Pessetto Zhihe Zang Xingliang Xie Ling Zhong Qing Su Wang Zan Xiurong Gao Yan Zhao Yiyi Sun Casitas B-Lineage Lymphoma RING Domain Inhibitors Protect Mice against High-Fat Diet-Induced Obesity and Insulin Resistance. PLoS ONE |
| title | Casitas B-Lineage Lymphoma RING Domain Inhibitors Protect Mice against High-Fat Diet-Induced Obesity and Insulin Resistance. |
| title_full | Casitas B-Lineage Lymphoma RING Domain Inhibitors Protect Mice against High-Fat Diet-Induced Obesity and Insulin Resistance. |
| title_fullStr | Casitas B-Lineage Lymphoma RING Domain Inhibitors Protect Mice against High-Fat Diet-Induced Obesity and Insulin Resistance. |
| title_full_unstemmed | Casitas B-Lineage Lymphoma RING Domain Inhibitors Protect Mice against High-Fat Diet-Induced Obesity and Insulin Resistance. |
| title_short | Casitas B-Lineage Lymphoma RING Domain Inhibitors Protect Mice against High-Fat Diet-Induced Obesity and Insulin Resistance. |
| title_sort | casitas b lineage lymphoma ring domain inhibitors protect mice against high fat diet induced obesity and insulin resistance |
| url | http://europepmc.org/articles/PMC4546618?pdf=render |
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