Advertisement

 

 

Human cytomegalovirus IE1 downregulates Hes1 in neural progenitor cells as a potential E3 ubiquitin ligase.

Human cytomegalovirus IE1 downregulates Hes1 in neural progenitor cells as a potential E3 ubiquitin ligase.
Author Information (click to view)

Liu XJ, Yang B, Huang SN, Wu CC, Li XJ, Cheng S, Jiang X, Hu F, Ming YZ, Nevels M, Britt WJ, Rayner S, Tang Q, Zeng WB, Zhao F, Luo MH,


Liu XJ, Yang B, Huang SN, Wu CC, Li XJ, Cheng S, Jiang X, Hu F, Ming YZ, Nevels M, Britt WJ, Rayner S, Tang Q, Zeng WB, Zhao F, Luo MH, (click to view)

Liu XJ, Yang B, Huang SN, Wu CC, Li XJ, Cheng S, Jiang X, Hu F, Ming YZ, Nevels M, Britt WJ, Rayner S, Tang Q, Zeng WB, Zhao F, Luo MH,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

PLoS pathogens 2017 07 2713(7) e1006542 doi 10.1371/journal.ppat.1006542
Abstract

Congenital human cytomegalovirus (HCMV) infection is the leading cause of neurological disabilities in children worldwide, but the mechanisms underlying these disorders are far from well-defined. HCMV infection has been shown to dysregulate the Notch signaling pathway in human neural progenitor cells (NPCs). As an important downstream effector of Notch signaling, the transcriptional regulator Hairy and Enhancer of Split 1 (Hes1) is essential for governing NPC fate and fetal brain development. In the present study, we report that HCMV infection downregulates Hes1 protein levels in infected NPCs. The HCMV 72-kDa immediate-early 1 protein (IE1) is involved in Hes1 degradation by assembling a ubiquitination complex and promoting Hes1 ubiquitination as a potential E3 ubiquitin ligase, followed by proteasomal degradation of Hes1. Sp100A, an important component of PML nuclear bodies, is identified to be another target of IE1-mediated ubiquitination. A C-terminal acidic region in IE1, spanning amino acids 451 to 475, is required for IE1/Hes1 physical interaction and IE1-mediated Hes1 ubiquitination, but is dispensable for IE1/Sp100A interaction and ubiquitination. Our study suggests a novel mechanism linking downregulation of Hes1 protein to neurodevelopmental disorders caused by HCMV infection. Our findings also complement the current knowledge of herpesviruses by identifying IE1 as the first potential HCMV-encoded E3 ubiquitin ligase.

Submit a Comment

Your email address will not be published. Required fields are marked *

7 − 5 =

[ HIDE/SHOW ]