An auto-regulatory loop for EBV LMP2A involves activation of Notch

Leah J. Anderson, Richard Longnecker*

*Corresponding author for this work

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

LMP2A is consistently detected in Hodgkin's lymphoma, nasopharyngeal carcinoma and has also been detected in Burkitt's lymphoma. Interestingly, LMP2A is detected in the absence of the transcriptional activator EBNA2, suggesting that an alternative mechanism is responsible for LMP2A expression. The intracellular domain of Notch (Notch-IC) and EBNA2 are functional homologs and recent microarray analysis indicates that LMP2A may constitutively activate the Notch pathway in vivo. Coupled with evidence that Notch-IC can bind to and activate the LMP2A promoter, we hypothesized that expression of LMP2A results in the constitutive activation of the Notch pathway to auto-regulate its promoter. Our data indicate that LMP2A constitutively activates the Notch pathway in B cells and epithelial cells. Expression of LMP2A alone is sufficient to activate its own expression and the amino-terminal signaling domain is required as LMP2B is unable to activate the LMP2A promoter. In addition, point mutations in tyrosines 31, 101 and 112 each results in a significant decrease in LMP2A promoter activation. Deletion of the RBP-Jκ consensus sequences results in a significant decrease in promoter activity. The observation that LMP2A activates its own promoter suggests that LMP2A exploits the Notch pathway in order to control its own expression and may explain EBNA2-independent expression of LMP2A in EBV-associated malignancies.

Original languageEnglish (US)
Pages (from-to)257-266
Number of pages10
JournalVirology
Volume371
Issue number2
DOIs
StatePublished - Feb 20 2008

Keywords

  • EBV
  • LMP2A
  • Notch
  • RBP-Jκ

ASJC Scopus subject areas

  • Virology

Fingerprint Dive into the research topics of 'An auto-regulatory loop for EBV LMP2A involves activation of Notch'. Together they form a unique fingerprint.

  • Cite this