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Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity
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; Ge, F (reprint author), Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China.
2013-10-01
Source PublicationMOLECULAR & CELLULAR PROTEOMICS
ISSN1535-9476
Volume12Issue:10Pages:2804-2819
AbstractBcl2-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.; 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.
SubtypeArticle
KeywordProtein-quality Control Heat-shock Proteins Large Gene Lists Quantitative-analysis Interaction Networks Virus Replication Knockdown Quick Bag3 Complex Degradation
Department[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
DOI10.1074/mcp.M112.025882
Funding OrganizationState 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 ; 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 ; 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 ; 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
Indexed BySCI
Language英语
WOS IDWOS:000330537000011
WOS KeywordPROTEIN-QUALITY CONTROL ; HEAT-SHOCK PROTEINS ; LARGE GENE LISTS ; QUANTITATIVE-ANALYSIS ; INTERACTION NETWORKS ; VIRUS REPLICATION ; KNOCKDOWN QUICK ; BAG3 ; COMPLEX ; DEGRADATION
Funding OrganizationState 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 ; 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 ; 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 ; 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
Citation statistics
Cited Times:39[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/19982
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorGe, F (reprint author), Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China.
Affiliation1.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
GB/T 7714
Chen, Ying,Yang, Li-Na,Cheng, Li,et al. Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity[J]. MOLECULAR & CELLULAR PROTEOMICS,2013,12(10):2804-2819.
APA Chen, Ying.,Yang, Li-Na.,Cheng, Li.,Tu, Shun.,Guo, Shu-Juan.,...&Ge, F .(2013).Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity.MOLECULAR & CELLULAR PROTEOMICS,12(10),2804-2819.
MLA Chen, Ying,et al."Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity".MOLECULAR & CELLULAR PROTEOMICS 12.10(2013):2804-2819.
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