TMEM2 binds to CSNK2A3 to inhibit HBV infection via activation of the JAK/STAT pathway.
Brain
/ metabolism
Carcinoma, Hepatocellular
/ complications
Case-Control Studies
Casein Kinase II
/ genetics
Epilepsy, Temporal Lobe
/ genetics
Hepatitis B
/ metabolism
Hepatitis B virus
/ physiology
Humans
Janus Kinase 1
/ genetics
Liver Neoplasms
/ complications
Membrane Proteins
/ genetics
PPAR gamma
/ genetics
STAT Transcription Factors
/ genetics
Tumor Cells, Cultured
CSNK2A3
HBV
HBV infection
JAK1-STAT
TMEM2
Journal
Experimental cell research
ISSN: 1090-2422
Titre abrégé: Exp Cell Res
Pays: United States
ID NLM: 0373226
Informations de publication
Date de publication:
01 03 2021
01 03 2021
Historique:
received:
05
08
2020
revised:
25
01
2021
accepted:
04
02
2021
pubmed:
15
2
2021
medline:
31
8
2021
entrez:
14
2
2021
Statut:
ppublish
Résumé
To investigate mechanisms that TMEM2 activation inhibits hepatitis B virus (HBV) infection in hepatocarcinoma (HCC) cells, co-immunoprecipitation (Co-IP) and mass spectrometry were used in screening interacting proteins for TMEM2. Levels of casein kinase 2 subunit α3 (CSNK2A3) in HCC cells were found to be inhibited or overexpressed using siRNAs and pcDNA3.1-CSNK2A3, respectively. Effect of CSNK2A3 expression on cell proliferation was analyzed using MTS, while its effect on HBV infection was measured using ddPCR and IHC. Western blotting and JAK inhibitor ruxolitinib were also used to determine whether TMEM2-regulated CSNK2A3 expression and HBV infection were affected by JAK-STAT signaling. Co-IP and mass spectrometry results showed that CSNK2A3 interacts with TMEM2. Moreover, overexpression of CSNK2A3 significantly inhibited cell proliferation, while inhibition of CSNK2A3 promoted proliferation of HCC cells. In addition, overexpression of CSNK2A3 was observed to significantly enhance HBV infection, while siRNA knockdown of CSNK2A3 inhibited HBV infection. Notably, effect of CSNK2A3 overexpression on HBV infection was suppressed by TMEM2 overexpression. Further mechanistic analyses have revealed that TMEM2 could antagonize the effects of CSNK2A3 on cell proliferation and HBV infection via JAK-STAT pathway activation. In conclusion, TMEM2 has been determined to bind to CSNK2A3 to inhibit HBV infection via activation of the JAK-STAT pathway.
Identifiants
pubmed: 33582094
pii: S0014-4827(21)00048-3
doi: 10.1016/j.yexcr.2021.112517
pii:
doi:
Substances chimiques
CEMIP2 protein, human
0
Membrane Proteins
0
PPAR gamma
0
STAT Transcription Factors
0
JAK1 protein, human
EC 2.7.10.2
Janus Kinase 1
EC 2.7.10.2
Casein Kinase II
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
112517Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.