Peroxisome proliferator-activated receptor β/δ cross talks with E2F and attenuates mitosis in HRAS-expressing cells.
Peroxisome proliferator-activated receptor β/δ cross talks with E2F and attenuates mitosis in HRAS-expressing cells.
复制标题
过氧化物酶体增殖物激活受体 β/β 与 E2F 交叉对话并减弱 HRAS 表达细胞的有丝分裂。
DOI：
10.1128/mcb.00092-12
复制
发表时间：
2012
影响因子：
5.3
通讯作者：
Peters,JeffreyM
中科院分区：
文献类型：
--
作者：
Zhu,Bokai;Khozoie,Combiz;Bility,MosesT;Ferry,ChristinaH;Blazanin,Nicholas;Glick,AdamB;Gonzalez,FrankJ;Peters,JeffreyM
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 theHrasoncogene by inducing a mitotic block. Mitosis-related genes that are predominantly regulated by E2F were induced to a higher level in HRAS-expressingPparβ/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.
