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

23 Citations (Scopus)

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
Pages (from-to)3687-3699
Number of pages13
JournalMolecular and Cellular Biology
Volume29
Issue number13
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

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Oncogenes
Fibroblasts
Neoplasms
Carcinogenesis
Transcription Factors
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

ELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to promote transformation. / Sashida, Goro; Liu, Yan; Elf, Shannon; Miyata, Yasuhiko; Ohyashiki, Kazuma; Izumi, Miki; Menendez, Silvia; Nimer, Stephen D.

In: Molecular and Cellular Biology, Vol. 29, No. 13, 01.07.2009, p. 3687-3699.

Research output: Contribution to journalArticle

Sashida, Goro ; Liu, Yan ; Elf, Shannon ; Miyata, Yasuhiko ; Ohyashiki, Kazuma ; Izumi, Miki ; Menendez, Silvia ; Nimer, Stephen D. / ELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to promote transformation. In: Molecular and Cellular Biology. 2009 ; Vol. 29, No. 13. pp. 3687-3699.
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AU - Menendez, Silvia

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