The N terminus of orf virus-encoded protein 002 inhibits acetylation of NF-κB p65 by preventing Ser(276) phosphorylation.
Orf virus-encoded protein 002 (ORFV002) inhibits NF-κB signaling pathway by decreasing the acetylation of NF-κB-p65 through interference of NF-κB p65's association with NF-κB p300. However, the precise mechanism of how ORFV002 interferes with the NF-κB p65/p300 association is still unknown. Due...
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oai:doaj.org-article:a8d2b3ce84804c28a507bd7053c1e5c92021-11-18T07:53:56ZThe N terminus of orf virus-encoded protein 002 inhibits acetylation of NF-κB p65 by preventing Ser(276) phosphorylation.1932-620310.1371/journal.pone.0058854https://doaj.org/article/a8d2b3ce84804c28a507bd7053c1e5c92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23536830/?tool=EBIhttps://doaj.org/toc/1932-6203Orf virus-encoded protein 002 (ORFV002) inhibits NF-κB signaling pathway by decreasing the acetylation of NF-κB-p65 through interference of NF-κB p65's association with NF-κB p300. However, the precise mechanism of how ORFV002 interferes with the NF-κB p65/p300 association is still unknown. Due to similarities of the amino acid sequences of ORFV002 and the adenovirus type 12 (Ad12) E1A protein (E1A-12), we hypothesized that the N-terminal 52 amino acids of ORFV002 might play an important role in this inhibition and constructed several in-frame fusions of ORFV002 to an enhanced green fluorescent protein (EGFP) reporter, including C-terminal and N-terminal deletion mutants of ORFV002. When the N-terminus of ORFV002 was absent, the localization of ORFV002 shifted mainly from the nucleus to the cytoplasm, and it's inhibition of NF-κB transactivation was lost. NF-κB p65 Lys(310) acetylation and Ser(276) phosphorylation were detected in co-transfection experiments with NF-κB p65 and ORFV002 or its mutants with, or without, the N-terminal region. The results showed that the N-terminus of ORFV002 plays a crucial role in inhibiting both the acetylation and phosphorylation of NF-κB p65. Further investigation indicated that ORFV002 and its C-terminal deletion mutants interfered with NF-κB p65 (Ser(276)) phosphorylation induced by mitogen- and stress-activated protein kinase-1 (MSK1) and the interaction between NF-κB p65 and MSK1. Since phosphorylated NF-κB p65 recruits transcriptional co-activators such as p300 and CBP, we concluded that the N-terminus of ORFV002 inhibits acetylation of NF-κB p65 by blocking phosphorylation of NF-κB p65 at Ser(276).Zhangyong NingZewei ZhengWenbo HaoChaohui DuanWei LiYuanyuan WangMing LiShuhong LuoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58854 (2013) |
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Medicine R Science Q Zhangyong Ning Zewei Zheng Wenbo Hao Chaohui Duan Wei Li Yuanyuan Wang Ming Li Shuhong Luo The N terminus of orf virus-encoded protein 002 inhibits acetylation of NF-κB p65 by preventing Ser(276) phosphorylation. |
| description |
Orf virus-encoded protein 002 (ORFV002) inhibits NF-κB signaling pathway by decreasing the acetylation of NF-κB-p65 through interference of NF-κB p65's association with NF-κB p300. However, the precise mechanism of how ORFV002 interferes with the NF-κB p65/p300 association is still unknown. Due to similarities of the amino acid sequences of ORFV002 and the adenovirus type 12 (Ad12) E1A protein (E1A-12), we hypothesized that the N-terminal 52 amino acids of ORFV002 might play an important role in this inhibition and constructed several in-frame fusions of ORFV002 to an enhanced green fluorescent protein (EGFP) reporter, including C-terminal and N-terminal deletion mutants of ORFV002. When the N-terminus of ORFV002 was absent, the localization of ORFV002 shifted mainly from the nucleus to the cytoplasm, and it's inhibition of NF-κB transactivation was lost. NF-κB p65 Lys(310) acetylation and Ser(276) phosphorylation were detected in co-transfection experiments with NF-κB p65 and ORFV002 or its mutants with, or without, the N-terminal region. The results showed that the N-terminus of ORFV002 plays a crucial role in inhibiting both the acetylation and phosphorylation of NF-κB p65. Further investigation indicated that ORFV002 and its C-terminal deletion mutants interfered with NF-κB p65 (Ser(276)) phosphorylation induced by mitogen- and stress-activated protein kinase-1 (MSK1) and the interaction between NF-κB p65 and MSK1. Since phosphorylated NF-κB p65 recruits transcriptional co-activators such as p300 and CBP, we concluded that the N-terminus of ORFV002 inhibits acetylation of NF-κB p65 by blocking phosphorylation of NF-κB p65 at Ser(276). |
| format |
article |
| author |
Zhangyong Ning Zewei Zheng Wenbo Hao Chaohui Duan Wei Li Yuanyuan Wang Ming Li Shuhong Luo |
| author_facet |
Zhangyong Ning Zewei Zheng Wenbo Hao Chaohui Duan Wei Li Yuanyuan Wang Ming Li Shuhong Luo |
| author_sort |
Zhangyong Ning |
| title |
The N terminus of orf virus-encoded protein 002 inhibits acetylation of NF-κB p65 by preventing Ser(276) phosphorylation. |
| title_short |
The N terminus of orf virus-encoded protein 002 inhibits acetylation of NF-κB p65 by preventing Ser(276) phosphorylation. |
| title_full |
The N terminus of orf virus-encoded protein 002 inhibits acetylation of NF-κB p65 by preventing Ser(276) phosphorylation. |
| title_fullStr |
The N terminus of orf virus-encoded protein 002 inhibits acetylation of NF-κB p65 by preventing Ser(276) phosphorylation. |
| title_full_unstemmed |
The N terminus of orf virus-encoded protein 002 inhibits acetylation of NF-κB p65 by preventing Ser(276) phosphorylation. |
| title_sort |
n terminus of orf virus-encoded protein 002 inhibits acetylation of nf-κb p65 by preventing ser(276) phosphorylation. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/a8d2b3ce84804c28a507bd7053c1e5c9 |
| work_keys_str_mv |
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| _version_ |
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