ChREBP, a glucose-responsive transcriptional factor, enhances glucose metabolism to support biosynthesis in human cytomegalovirus-infected cells.
Proc Natl Acad Sci U S A
; 111(5): 1951-6, 2014 Feb 04.
Article
em En
| MEDLINE
| ID: mdl-24449882
ABSTRACT
Carbohydrate-response element binding protein (ChREBP) plays a key role in regulating glucose metabolism and de novo lipogenesis in metabolic tissues and cancer cells. Here we report that ChREBP is also a critical regulator of the metabolic alterations induced during human cytomegalovirus (HCMV) infection. The expression of both ChREBP-α and ChREBP-ß is robustly induced in HCMV-infected human fibroblasts; this induction is required for efficient HCMV infection. Depletion of ChREBP in HCMV-infected cells results in reduction of HCMV-induced glucose transporter 4 and glucose transporter 2 expression, leading to inhibition of glucose uptake, lactate production, nucleotide biosynthesis, and NADPH generation. We previously reported that HCMV infection induces lipogenesis through the activation of sterol regulatory element binding protein 1, which is mediated by the induction of PKR-like endoplasmic reticulum kinase. Data from the present study show that HCMV-induced lipogenesis is also controlled by the induction of ChREBP, in a second mechanism involved in the regulation of HCMV-induced de novo lipogenesis. These results suggest that ChREBP plays a key role in reprogramming glucose and lipid metabolism in HCMV infection.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Citomegalovirus
/
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos
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Lipogênese
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Fibroblastos
/
Glucose
/
Nucleotídeos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article