The N terminus of orf virus-encoded protein 002 inhibits acetylation of NF-κB p65 by preventing Ser(276) phosphorylation.
The N terminus of orf virus-encoded protein 002 inhibits acetylation of NF-κB p65 by preventing Ser(276) phosphorylation.
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DOI：
10.1371/journal.pone.0058854
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Luo S
中科院分区：
文献类型：
--
作者：
Ning Z;Zheng Z;Hao W;Duan C;Li W;Wang Y;Li M;Luo S
Orf病毒编码蛋白002（ORFV 002）通过干扰NF-κ B p300与NF-κ B B p65的结合，降低NF-κ B-p65的乙酰化水平，从而抑制NF-κB B信号通路。然而，ORFV 002如何干扰NF-κB p65/p300缔合的精确机制仍然未知。由于ORFV 002和腺病毒12型（Ad 12）E1 A蛋白（E1 A-12）的氨基酸序列相似，我们假设ORFV 002的N-末端52个氨基酸可能在这种抑制中起重要作用，并构建了ORFV 002与增强型绿色荧光蛋白（EGFP）报告基因的几种框内融合体，包括ORFV 002的C末端和N末端缺失突变体。当ORFV 002 N端缺失时，ORFV 002的定位主要由核向胞浆转移，对NF-κB转录的抑制作用丧失。在NF-κ B p65和ORFV 002或其突变体（有或没有N-末端区域）的共转染实验中检测NF-κ B p65 Lys 310乙酰化和Ser 276磷酸化。结果表明，ORFV 002的N端在抑制NF-κB p65的乙酰化和磷酸化中起着重要作用。进一步的研究表明ORFV 002及其C端缺失突变体干扰了丝裂原和应激活化蛋白激酶1（MSK 1）诱导的NF-κB p65（Ser 276）磷酸化以及NF-κB p65和MSK 1之间的相互作用。由于磷酸化的NF-κB p65募集转录共激活因子如p300和CBP，我们得出结论，ORFV 002的N末端通过阻断NF-κ B p65在Ser 276的磷酸化来抑制NF-κ B p65的乙酰化。
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 Lys310 acetylation and Ser276 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 (Ser276) 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 Ser276.
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影响因子：
5
作者：
Mercer, AA;Norihito, UA;Fleming, SB
通讯作者：
Fleming, SB
影响因子：
5.4
作者：
Diel, D. G.;Delhon, G.;Rock, D. L.
通讯作者：
Rock, D. L.
影响因子：
5.4
作者：
Jiao, Junfang;Guan, Hancheng;Ricciardi, Robert P.
通讯作者：
Ricciardi, Robert P.
DOI：
10.1007/bf01249692
发表时间：
1974-01-01
期刊：
ARCHIV FUR DIE GESAMTE VIRUSFORSCHUNG
影响因子：
--
作者：
MCCLURKIN, AW;PIRTLE, EC;SMITH, RL
通讯作者：
SMITH, RL
影响因子：
4.8
作者：
Gao, Nan;Asamitsu, Kaori;Okamoto, Takashi
通讯作者：
Okamoto, Takashi