ELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to promote transformation

Goro Sashida, Yan Liu, Shannon Elf, Yasuhiko Miyata, Kazuma Ohyashiki, Miki Izumi, Silvia Menendez, Stephen D. Nimer

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Several ETS transcription factors, including ELF4/MEF, can function as oncogenes in murine cancer models and are overexpressed in human cancer. We found that Elf4/Mef activates Mdm2 expression; thus, lack of or knockdown of Elf4/Mef reduces Mdm2 levels in mouse embryonic fibroblasts (mef's), leading to enhanced p53 protein accumulation and p53-dependent senescence. Even though p53 is absent in Elf4-/- p53-/- mef's, neither oncogenic H-RasV12 nor c-myc can induce transformation of these cells. This appears to relate to the INK4a/ARF locus; both p19ARF and p16 are increased in Elf4-/- p53-/- mef's, and expression of Bmi-1 or knockdown of p16 in this context restores H-RasV12-induced transformation. Thus, ELF4/MEF promotes tumorigenesis by inhibiting both the p53 and p16/Rb pathways.

Original languageEnglish (US)
Pages (from-to)3687-3699
Number of pages13
JournalMolecular and cellular biology
Volume29
Issue number13
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'ELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to promote transformation'. Together they form a unique fingerprint.

  • Cite this

    Sashida, G., Liu, Y., Elf, S., Miyata, Y., Ohyashiki, K., Izumi, M., Menendez, S., & Nimer, S. D. (2009). ELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to promote transformation. Molecular and cellular biology, 29(13), 3687-3699. https://doi.org/10.1128/MCB.01551-08