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| 題名: | INTERACTION BETWEEN OV20.0 AND ADENOSINE DEAMINASES ACTING ON RNA 1 |
| 作者: | Liao, Guan-Ru;Lin, Fong-Yuan;Yeu-Yang;Tseng;Hsu, Wei-Li |
| 關鍵詞: | ADAR1;orf virus;OV20.0 |
| 日期: | 2017-11-03 |
| 上傳時間: | 2017-11-08T03:37:05Z (UTC)
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| 摘要: | Objectives: Orf virus (ORFV) OV20.0 is an important virulent factor. By interacting with protein kinase R (PKR) and its activator,
namely PACT, OV20.0 inhibits PKR activation to promote virus replication. OV20.0, PKR and PACT all harbor dsRNA binding
domains (DRBDs) and are classified as dsRNA binding proteins (DRBPs). It has been proposed that DRBPs regulate cell physiology
by formation of protein dimer. A DRBP, designated adenosine deaminases acting on RNA 1 (ADAR1), catalyzes deamination of
adenosine (A) to produce inosine (I) in dsRNA substrate in nucleus. Due to its nature of binding dsRNA, we postulated that OV20.0
possibly interacts with ADAR1. Therefore, we studied the impact of OV20.0 on cellular function of ADAR1 and their effects on
ORFV pathogenesis.
Methods: Immunoprecipitation was performed to identify cellular proteins interacting with OV20.0. A series of constructs
containing deletions of individual functional domains were used to determine the minimal criterial for intermolecular interaction are
determined. To further confirm their cellular distribution, transient expression of GFP-tagged OV20.0 and mCherry-tagged ADAR1
followed by immunofluorescence assay was performed.
Results: In current study, association of ADAR1 with OV20.0 was evidenced for the first time. Consistently, C-terminal DRBD of
OV20.0, and the first DRBD of ADAR1 are critical for this interaction. Furthermore, we found mCherry-tagged ADAR1 colocalized
with two OV20.0 isoforms, the full length and N terminal truncated OV20.0 (sh20), in nucleus. Interestingly, ARAD1 was also
shuttled to cytoplasm in the proximity of sh20 in a subset of cells that indicates the interaction between ADAR1 and sh20 possibly
alters their cellular distribution.
Conclusion: OV20.0 associates with cellular ADAR1 protein via their DRBD. Furthermore, among the three DRBDs, the first
DRBD of ADAR1 is critical for their interaction. The consequence of interaction leads to re-distribution of ADAR1 to cytoplasm,
indicating that OV20.0 possibly influences the function of ADAR1. |
| 顯示於類別: | [美容系] 期刊論文
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