| First Author | Zhu B | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 11 | Pages | 2065-82 |
| PubMed ID | 22473992 | Mgi Jnum | J:185722 |
| Mgi Id | MGI:5429785 | Doi | 10.1128/MCB.00092-12 |
| Citation | Zhu B, et al. (2012) Peroxisome proliferator-activated receptor beta/delta cross talks with E2F and attenuates mitosis in HRAS-expressing cells. Mol Cell Biol 32(11):2065-82 |
| abstractText | The role of peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) in Harvey sarcoma ras (Hras)-expressing cells was examined. Ligand activation of PPARbeta/delta 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 Pparbeta/delta-null keratinocytes compared to HRAS-expressing wild-type keratinocytes. Ligand-activated PPARbeta/delta 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 PPARbeta/delta cross talk with E2F signaling. Since cotreatment with a PPARbeta/delta ligand and various mitosis inhibitors increases the efficacy of increasing G(2)/M arrest, targeting PPARbeta/delta in conjunction with mitosis inhibitors could become a suitable option for development of new multitarget strategies for inhibiting RAS-dependent tumorigenesis. |
