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题名: Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity
作者: Chen, Ying1, 2; Yang, Li-Na3, 4; Cheng, Li3, 4; Tu, Shun3, 4; Guo, Shu-Juan3, 4; Le, Huang-Ying3; Xiong, Qian1; Mo, Ran1, 2; Li, Chong-Yang1, 2; Jeong, Jun-Seop5, 6; Jiang, Lizhi6, 7; Blackshaw, Seth6, 7; Bi, Li-Jun8; Zhu, Heng5, 6; Tao, Sheng-Ce3, 4, 9; Ge, Feng1
通讯作者: Ge, F (reprint author), Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China.
关键词: PROTEIN-QUALITY CONTROL ; HEAT-SHOCK PROTEINS ; LARGE GENE LISTS ; QUANTITATIVE-ANALYSIS ; INTERACTION NETWORKS ; VIRUS REPLICATION ; KNOCKDOWN QUICK ; BAG3 ; COMPLEX ; DEGRADATION
刊名: MOLECULAR & CELLULAR PROTEOMICS
发表日期: 2013-10-01
DOI: 10.1074/mcp.M112.025882
卷: 12, 期:10, 页:2804-2819
收录类别: SCI
文章类型: Article
部门归属: [Chen, Ying ; Xiong, Qian ; Mo, Ran ; Li, Chong-Yang ; Ge, Feng] Chinese Acad Sci, Inst Hydrobiol, Key Lab Algal Biol, Wuhan 430072, Hubei, Peoples R China ; [Chen, Ying ; Mo, Ran ; Li, Chong-Yang] Univ Chinese Acad Sci, Beijing 100039, Peoples R China ; [Yang, Li-Na ; Cheng, Li ; Tu, Shun ; Guo, Shu-Juan ; Le, Huang-Ying ; Tao, Sheng-Ce] Shanghai Jiao Tong Univ, Key Lab Syst Biomed, Minist Educ, Shanghai Ctr Syst Biomed, Shanghai 200240, Peoples R China ; [Yang, Li-Na ; Cheng, Li ; Tu, Shun ; Guo, Shu-Juan ; Tao, Sheng-Ce] State Key Lab Oncogenes & Related Genes, Shanghai 200240, Peoples R China ; [Jeong, Jun-Seop ; Zhu, Heng] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA ; [Jeong, Jun-Seop ; Jiang, Lizhi ; Blackshaw, Seth ; Zhu, Heng] Johns Hopkins Univ, Sch Med, High Throughput Biol Ctr, Baltimore, MD 21205 USA ; [Jiang, Lizhi ; Blackshaw, Seth] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA ; [Bi, Li-Jun] Chinese Acad Sci, Inst Biophys, Key Lab Noncoding RNA, Beijing 100101, Peoples R China ; [Tao, Sheng-Ce] Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200240, Peoples R China
资助者: State Key Development Program for Basic Research in China [2012CB518700, 2010CB529205]; National High Technology Research and Development Program of China [2012AA020103, 2012AA020203]; National Natural Science Foundation of China [31000388]; Hundred Talents Program of the Chinese Academy of Sciences
摘要: Bcl2-associated athanogene 3 (BAG3), a member of the BAG family of co-chaperones, plays a critical role in regulating apoptosis, development, cell motility, autophagy, and tumor metastasis and in mediating cell adaptive responses to stressful stimuli. BAG3 carries a BAG domain, a WW domain, and a proline-rich repeat (PXXP), all of which mediate binding to different partners. To elucidate BAG3's interaction network at the molecular level, we employed quantitative immunoprecipitation combined with knockdown and human proteome microarrays to comprehensively profile the BAG3 interactome in humans. We identified a total of 382 BAG3-interacting proteins with diverse functions, including transferase activity, nucleic acid binding, transcription factors, proteases, and chaperones, suggesting that BAG3 is a critical regulator of diverse cellular functions. In addition, we characterized interactions between BAG3 and some of its newly identified partners in greater detail. In particular, bioinformatic analysis revealed that the BAG3 interactome is strongly enriched in proteins functioning within the proteasome-ubiquitination process and that compose the proteasome complex itself, suggesting that a critical biological function of BAG3 is associated with the proteasome. Functional studies demonstrated that BAG3 indeed interacts with the proteasome and modulates its activity, sustaining cell survival and underlying resistance to therapy through the down-modulation of apoptosis. Taken as a whole, this study expands our knowledge of the BAG3 interactome, provides a valuable resource for understanding how BAG3 affects different cellular functions, and demonstrates that biologically relevant data can be harvested using this kind of integrated approach.
英文摘要: Bcl2-associated athanogene 3 (BAG3), a member of the BAG family of co-chaperones, plays a critical role in regulating apoptosis, development, cell motility, autophagy, and tumor metastasis and in mediating cell adaptive responses to stressful stimuli. BAG3 carries a BAG domain, a WW domain, and a proline-rich repeat (PXXP), all of which mediate binding to different partners. To elucidate BAG3's interaction network at the molecular level, we employed quantitative immunoprecipitation combined with knockdown and human proteome microarrays to comprehensively profile the BAG3 interactome in humans. We identified a total of 382 BAG3-interacting proteins with diverse functions, including transferase activity, nucleic acid binding, transcription factors, proteases, and chaperones, suggesting that BAG3 is a critical regulator of diverse cellular functions. In addition, we characterized interactions between BAG3 and some of its newly identified partners in greater detail. In particular, bioinformatic analysis revealed that the BAG3 interactome is strongly enriched in proteins functioning within the proteasome-ubiquitination process and that compose the proteasome complex itself, suggesting that a critical biological function of BAG3 is associated with the proteasome. Functional studies demonstrated that BAG3 indeed interacts with the proteasome and modulates its activity, sustaining cell survival and underlying resistance to therapy through the down-modulation of apoptosis. Taken as a whole, this study expands our knowledge of the BAG3 interactome, provides a valuable resource for understanding how BAG3 affects different cellular functions, and demonstrates that biologically relevant data can be harvested using this kind of integrated approach.
关键词[WOS]: PROTEIN-QUALITY CONTROL ; HEAT-SHOCK PROTEINS ; LARGE GENE LISTS ; QUANTITATIVE-ANALYSIS ; INTERACTION NETWORKS ; VIRUS REPLICATION ; KNOCKDOWN QUICK ; BAG3 ; COMPLEX ; DEGRADATION
语种: 英语
WOS记录号: WOS:000330537000011
ISSN号: 1535-9476
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/19982
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, Key Lab Algal Biol, Wuhan 430072, Hubei, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100039, Peoples R China
3.Shanghai Jiao Tong Univ, Key Lab Syst Biomed, Minist Educ, Shanghai Ctr Syst Biomed, Shanghai 200240, Peoples R China
4.State Key Lab Oncogenes & Related Genes, Shanghai 200240, Peoples R China
5.Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA
6.Johns Hopkins Univ, Sch Med, High Throughput Biol Ctr, Baltimore, MD 21205 USA
7.Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
8.Chinese Acad Sci, Inst Biophys, Key Lab Noncoding RNA, Beijing 100101, Peoples R China
9.Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200240, Peoples R China

Recommended Citation:
Chen, Ying; Yang, Li-Na; Cheng, Li; Tu, Shun; Guo, Shu-Juan; Le, Huang-Ying; Xiong, Qian; Mo, Ran; Li, Chong-Yang; Jeong, Jun-Seop; Jiang, Lizhi; Blackshaw, Seth; Bi, Li-Jun; Zhu, Heng; Tao, Sheng-Ce; Ge, Feng.Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity,MOLECULAR & CELLULAR PROTEOMICS,2013,12(10):2804-2819
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