TY - JOUR
T1 - ELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to promote transformation
AU - Sashida, Goro
AU - Liu, Yan
AU - Elf, Shannon
AU - Miyata, Yasuhiko
AU - Ohyashiki, Kazuma
AU - Izumi, Miki
AU - Menendez, Silvia
AU - Nimer, Stephen D.
PY - 2009/7
Y1 - 2009/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=67650072923&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67650072923&partnerID=8YFLogxK
U2 - 10.1128/MCB.01551-08
DO - 10.1128/MCB.01551-08
M3 - Article
C2 - 19380490
AN - SCOPUS:67650072923
SN - 0270-7306
VL - 29
SP - 3687
EP - 3699
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 13
ER -
