1. Academic Validation
  2. Nuclear LYRIC/AEG-1 interacts with PLZF and relieves PLZF-mediated repression

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

  • Oncogene. 2009 Oct 15;28(41):3663-70. doi: 10.1038/onc.2009.223.
H J Thirkettle 1 I G Mills H C Whitaker D E Neal
Affiliations

Affiliation

  • 1 Uro-Oncology Research Group, Cancer Research UK Cambridge Research Institute, Cambridge, UK.
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.

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