WW domain containing E3 ubiquitin protein ligase 1 (WWP1) negatively regulates TLR4-mediated TNF-α and IL-6 production by proteasomal degradation of TNF receptor associated factor 6 (TRAF6).
Toll-like receptors (TLRs) play a pivotal role in the defense against invading pathogens by detecting pathogen-associated molecular patterns (PAMPs). TLR4 recognizes lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria, resulting in the induction and secretion of proinflammatory cyt...
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| Format: | Article |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3684580?pdf=render |
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| author | Xiao-Wen Lin Wei-Cheng Xu Jian-Gang Luo Xue-Jiao Guo Tao Sun Xu-Li Zhao Zhi-Jian Fu |
| author_facet | Xiao-Wen Lin Wei-Cheng Xu Jian-Gang Luo Xue-Jiao Guo Tao Sun Xu-Li Zhao Zhi-Jian Fu |
| author_sort | Xiao-Wen Lin |
| collection | DOAJ |
| description | Toll-like receptors (TLRs) play a pivotal role in the defense against invading pathogens by detecting pathogen-associated molecular patterns (PAMPs). TLR4 recognizes lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria, resulting in the induction and secretion of proinflammatory cytokines such as TNF-α and IL-6. The WW domain containing E3 ubiquitin protein ligase 1 (WWP1) regulates a variety of cellular biological processes. Here, we investigated whether WWP1 acts as an E3 ubiquitin ligase in TLR-mediated inflammation.Knocking down WWP1 enhanced the TNF-α and IL-6 production induced by LPS, and over-expression of WWP1 inhibited the TNF-α and IL-6 production induced by LPS, but not by TNF-α. WWP1 also inhibited the IκB-α, NF-κB, and MAPK activation stimulated by LPS. Additionally, WWP1 could degrade TRAF6, but not IRAK1, in the proteasome pathway, and knocking down WWP1 reduced the LPS-induced K48-linked, but not K63-linked, polyubiquitination of endogenous TRAF6.We identified WWP1 as an important negative regulator of TLR4-mediated TNF-α and IL-6 production. We also showed that WWP1 functions as an E3 ligase when cells are stimulated with LPS by binding to TRAF6 and promoting K48-linked polyubiquitination. This results in the proteasomal degradation of TRAF6. |
| first_indexed | 2024-12-16T08:52:38Z |
| format | Article |
| id | doaj.art-d0179db6118147a09d209d30748bdc36 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T08:52:38Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d0179db6118147a09d209d30748bdc362022-12-21T22:37:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6763310.1371/journal.pone.0067633WW domain containing E3 ubiquitin protein ligase 1 (WWP1) negatively regulates TLR4-mediated TNF-α and IL-6 production by proteasomal degradation of TNF receptor associated factor 6 (TRAF6).Xiao-Wen LinWei-Cheng XuJian-Gang LuoXue-Jiao GuoTao SunXu-Li ZhaoZhi-Jian FuToll-like receptors (TLRs) play a pivotal role in the defense against invading pathogens by detecting pathogen-associated molecular patterns (PAMPs). TLR4 recognizes lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria, resulting in the induction and secretion of proinflammatory cytokines such as TNF-α and IL-6. The WW domain containing E3 ubiquitin protein ligase 1 (WWP1) regulates a variety of cellular biological processes. Here, we investigated whether WWP1 acts as an E3 ubiquitin ligase in TLR-mediated inflammation.Knocking down WWP1 enhanced the TNF-α and IL-6 production induced by LPS, and over-expression of WWP1 inhibited the TNF-α and IL-6 production induced by LPS, but not by TNF-α. WWP1 also inhibited the IκB-α, NF-κB, and MAPK activation stimulated by LPS. Additionally, WWP1 could degrade TRAF6, but not IRAK1, in the proteasome pathway, and knocking down WWP1 reduced the LPS-induced K48-linked, but not K63-linked, polyubiquitination of endogenous TRAF6.We identified WWP1 as an important negative regulator of TLR4-mediated TNF-α and IL-6 production. We also showed that WWP1 functions as an E3 ligase when cells are stimulated with LPS by binding to TRAF6 and promoting K48-linked polyubiquitination. This results in the proteasomal degradation of TRAF6.http://europepmc.org/articles/PMC3684580?pdf=render |
| spellingShingle | Xiao-Wen Lin Wei-Cheng Xu Jian-Gang Luo Xue-Jiao Guo Tao Sun Xu-Li Zhao Zhi-Jian Fu WW domain containing E3 ubiquitin protein ligase 1 (WWP1) negatively regulates TLR4-mediated TNF-α and IL-6 production by proteasomal degradation of TNF receptor associated factor 6 (TRAF6). PLoS ONE |
| title | WW domain containing E3 ubiquitin protein ligase 1 (WWP1) negatively regulates TLR4-mediated TNF-α and IL-6 production by proteasomal degradation of TNF receptor associated factor 6 (TRAF6). |
| title_full | WW domain containing E3 ubiquitin protein ligase 1 (WWP1) negatively regulates TLR4-mediated TNF-α and IL-6 production by proteasomal degradation of TNF receptor associated factor 6 (TRAF6). |
| title_fullStr | WW domain containing E3 ubiquitin protein ligase 1 (WWP1) negatively regulates TLR4-mediated TNF-α and IL-6 production by proteasomal degradation of TNF receptor associated factor 6 (TRAF6). |
| title_full_unstemmed | WW domain containing E3 ubiquitin protein ligase 1 (WWP1) negatively regulates TLR4-mediated TNF-α and IL-6 production by proteasomal degradation of TNF receptor associated factor 6 (TRAF6). |
| title_short | WW domain containing E3 ubiquitin protein ligase 1 (WWP1) negatively regulates TLR4-mediated TNF-α and IL-6 production by proteasomal degradation of TNF receptor associated factor 6 (TRAF6). |
| title_sort | ww domain containing e3 ubiquitin protein ligase 1 wwp1 negatively regulates tlr4 mediated tnf α and il 6 production by proteasomal degradation of tnf receptor associated factor 6 traf6 |
| url | http://europepmc.org/articles/PMC3684580?pdf=render |
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