Nuclear targeting of the betanodavirus B1 protein via two arginine-rich domains induces G1/S cell cycle arrest mediated by upregulation of p53/p21

Yu Chin Su, Latif Reshi, Lei Jia Chen, Wei Han Li, Hsuan Wen Chiu, Jiann Ruey Hong

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

The molecular functions of betanodavirus non-structural protein B and its role in host cell survival remain unclear. In the present study, we examined the roles of specific nuclear targeting domains in B1 localization as well as the effect of B1 nuclear localization on the cell cycle and host cell survival. The B1 protein of the Red spotted grouper nervous necrosis virus (RGNNV) was detected in GF-1 grouper cells as early as 24 hours post-infection (hpi). Using an EYFP-B1 fusion construct, we observed nuclear localization of the B1 protein (up to 99%) in GF-1 cells at 48 hpi. The nuclear localization of B1 was mediated by two arginine-rich nuclear targeting domains (B domain: 46RRSRR51; C domain: 63RDKRPRR70) and domain C was more important than domain B in this process. B1 nuclear localization correlated with upregulation of p53 and p21(wef1/cip1); downregulation of Cyclin D1, CDK4 and Mdm2; and G1/S cell cycle arrest in GF-1 cells. In conclusion, nuclear targeting of the RGNNV B1 protein via two targeting domains causes cell cycle arrest by up-regulating p53/p21 and down-regulating Mdm2, thereby regulating host cell survival.

Original languageEnglish
Article number3079
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

All Science Journal Classification (ASJC) codes

  • General

Fingerprint Dive into the research topics of 'Nuclear targeting of the betanodavirus B1 protein via two arginine-rich domains induces G1/S cell cycle arrest mediated by upregulation of p53/p21'. Together they form a unique fingerprint.

Cite this