Nuclear LYRIC/AEG-1 interacts with PLZF and relieves PLZF-mediated repression

H J Thirkettle, I G Mills, H C Whitaker, D E Neal

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

LYRIC/AEG-1 and its altered expression have been linked to carcinogenesis in prostate, brain and melanoma as well as promoting chemoresistance and metastasis in breast cancer. LYRIC/AEG-1 function remains unclear, although LYRIC/AEG-1 is activated by oncogenic HA-RAS, through binding of c-myc to its promoter, which in turn regulates the key components of the PI3-kinase and nuclear factor-kappaB pathways. We have identified the transcriptional repressor PLZF as an interacting protein of LYRIC/AEG through a yeast two-hybrid screen. PLZF regulates the expression of genes involved in cell growth and apoptosis including c-myc. Coexpression of LYRIC/AEG-1 with PLZF leads to a reduction in PLZF-mediated repression by reducing PLZF binding to promoters. We have confirmed that nuclear LYRIC/AEG-1 and PLZF interact in mammalian cells via the N- and C termini of LYRIC/AEG-1 and a region C terminal to the RD2 domain of PLZF. Both proteins colocalize to nuclear bodies containing histone deacetylases, which are known to promote PLZF-mediated repression. Our data suggest one mechanism for cells with altered LYRIC/AEG-1 expression to evade apoptosis and increase cell growth during tumourigenesis through the regulation of PLZF repression.

Original languageEnglish
Pages (from-to)3663-70
Number of pages8
JournalOncogene
Volume28
Issue number41
DOIs
Publication statusPublished - 15 Oct 2009

Keywords

  • Cell Adhesion Molecules
  • Cell Nucleus
  • Gene Expression Regulation
  • HeLa Cells
  • Histone Deacetylases
  • Humans
  • Kruppel-Like Transcription Factors
  • Protein Structure, Tertiary
  • RNA, Messenger
  • Transcription, Genetic

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