التفاصيل البيبلوغرافية
| العنوان: |
The Nuclear Receptor Peroxisome Proliferator-activated Receptor-β/δ (PPARβ/δ) Promotes Oncogene-induced Cellular Senescence through Repression of Endoplasmic Reticulum Stress. |
| المؤلفون: |
Xiang Zhao1, Kuja-Panula, Juha1, Sundvik, Maria1,2, Yu-Chia Chen1,2, Aho, Vilma3, Peltola, Marjaana A.1, Porkka-Heiskanen, Tarja3, Panula, Pertti1,2, Rauvala, Heikki1 heikki.rauvala@helsinki.fi |
| المصدر: |
Journal of Biological Chemistry. 7/18/2014, Vol. 289 Issue 29, p20102-20119. 18p. |
| مصطلحات موضوعية: |
*MEMBRANE proteins, *CELL adhesion molecules, *ZEBRA danio, *POTASSIUM channels, *NEURAL circuitry, *NEURONS, *ANIMAL cloning |
| مستخلص: |
Endoplasmic reticulum (ER) stress and ER stress-associated unfolded protein response (UPR) can promote cancer cell survival, but it remains unclear whether they can influence oncogene-induced senescence. The present study examined the role of ER stress in senescence using oncogene-dependent models. Increased ER stress attenuated senescence in part by up-regulating phosphorylated protein kinase B (p-AKT) and decreasing phosphorylated extracellular signal-regulated kinase (p-ERK). A positive feed forward loop between p-AKT, ER stress, and UPR was discovered whereby a transient increase of ER stress caused reduced senescence and promotion of tumorigenesis. Decreased ER stress was further correlated with increased senescence in both mouse and human tumors. Interestingly, H-RAS-expressing Pparβ/δ null cells and tumors having increased cell proliferation exhibited enhanced ER stress, decreased cellular senescence, and/or enhanced tumorigenicity. Collectively, these results demonstrate a new role for ER stress and UPR that attenuates H-RAS-induced senescence and suggest that PPARβ/δ can repress this oncogene-induced ER stress to promote senescence in accordance with its role as a tumor modifier that suppresses carcinogenesis. [ABSTRACT FROM AUTHOR] |
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