Journal
ONCOGENE
Volume 28, Issue 41, Pages 3663-3670Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.223
Keywords
LYRIC/AEG-1; PLZF; transcription; repression; nucleus
Funding
- Cancer Research UK
- Medical Research Council
- Cancer Research UK Cambridge Genomics Core Facility and Microscopy Core Facility
- Medical Research Council [G0500966] Funding Source: researchfish
- MRC [G0500966] Funding Source: UKRI
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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-kappa B 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. Oncogene (2009) 28, 3663-3670; doi:10.1038/onc.2009.223; published online 3 August 2009
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