Peroxisome proliferator-activated receptor β/δ cross talks with e2f and attenuates mitosis in HRAS-expressing cells

Bokai Zhu, Combiz Khozoie, Moses T. Bility, Christina H. Ferry, Nicholas Blazanin, Adam B. Glick, Frank J. Gonzalez, Jeffrey M. Peters

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The role of peroxisome proliferator-activated receptor (β/δ (PPARβ/δ) in Harvey sarcoma ras (Hras)-expressing cells was examined. Ligand activation of PPARβ/δ caused a negative selection with respect to cells expressing higher levels of the Hras oncogene by inducing a mitotic block. Mitosis-related genes that are predominantly regulated by E2F were induced to a higher level in HRAS-expressing Pparβ/δ-null keratinocytes compared to HRAS-expressing wild-type keratinocytes. Ligand-activated PPARβ/δ repressed expression of these genes by direct binding with p130/p107, facilitating nuclear translocation and increasing promoter recruitment of p130/p107. These results demonstrate a novel mechanism of PPARβ/δ cross talk with E2F signaling. Since cotreatment with a PPARβ/δ ligand and various mitosis inhibitors increases the efficacy of increasing G2/M arrest, targeting PPARβ/δ in conjunction with mitosis inhibitors could become a suitable option for development of new multitarget strategies for inhibiting RAS-dependent tumorigenesis.

Original languageEnglish (US)
Pages (from-to)2065-2082
Number of pages18
JournalMolecular and cellular biology
Issue number11
StatePublished - Jun 1 2012


All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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