Herpes simplex virus 1 α regulatory protein ICP0 functionally interacts with cellular transcription factor BMAL1

Yasushi Kawaguchi, Michiko Tanaka, Akihiko Yokoymama, Go Matsuda, Kentaro Kato, Hiroyuki Kagawa, Kanji Hirai, Bernard Roizman

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

The infected cell protein no. 0 (ICP0) of herpes simplex virus 1 (HSV-1) is a promiscuous transactivator shown to enhance the expression of gene introduced into cells by infection or transfection. At the molecular level, ICP0 is a 775-aa ring finger protein localized initially in the nucleus and late in infection in the cytoplasm and mediates the degradation of several proteins and stabilization of others. None of the known functions at the molecular level account for the apparent activity of ICP0 as a trans-activator. Here we report that ICP0 functionally interacts with cellular transcription factor BMAL1, a member of the basic helixloop-helix PER-ARNT-SIM (PAS) super family of transcriptional regulators. Specifically, sequences mapped to the exon II of ICP0 interacted with BMAL1 in the yeast two-hybrid system and in reciprocal pull-down experiments in vitro. Moreover, the enhancement of transcription of a luciferase reporter construct whose promoter contained multiple BMAL1-binding sites by ICP0 and BMAL1 was significantly greater than that observed by ICP0 or BMAL1 alone. Although the level of BMAL1 present in nuclei of infected cells remained unchanged between 3 and 8 h after infection, the level of cytoplasmic BMAL1 was reduced at 8 h after infection. The reduction of cytoplasmic BMAL1 was significantly greater in cells infected with the ICP0-null mutant than in the wild-type virus-infected cells, suggesting that ICP0 mediates partial stabilization of the protein. These results indicate that ICP0 interacts physically and functionally with at least one cellular transcription-regulatory factor.

Original languageEnglish
Pages (from-to)1877-1882
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number4
DOIs
Publication statusPublished - 2001 Feb 13
Externally publishedYes

ASJC Scopus subject areas

  • General

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