کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10757847 | 1050398 | 2013 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
RSK2-induced stress tolerance enhances cell survival signals mediated by inhibition of GSK3β activity
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Our previous studies demonstrated that RSK2 plays a key role in cell proliferation and transformation induced by tumor promoters such as epidermal growth factor (EGF) in mouse and human skin cells. However, no direct evidence has been found regarding the relationship of RSK2 and cell survival. In this study, we found that RSK2 interacted and phosphorylated GSK3β at Ser9. Notably, GSK3β phosphorylation at Ser9 was suppressed in RSK2â/â MEFs compared with RSK2+/+ MEFs by stimulation of EGF and calcium ionophore A23187, a cellular calcium stressor. In proliferation, we found that RSK2 deficiency suppressed cell proliferation compared with RSK2+/+ MEFs. In contrast, GSK3βâ/â MEFs induced the cell proliferation compared with GSK3β+/+ MEFs. Importantly, RSK2â/â MEFs were induced severe cellular morphology change by A23187 and enhanced G1/G0 and sub-G1 accumulation of the cell cycle phase compared with RSK2+/+ MEFs. The sub-G1 induction in RSK2â/â MEFs by A23187 was correlated with increase of cytochrome c release, caspase-3 cleavage and apoptotic DNA fragmentation compared with RSK2+/+ MEFs. Notably, return back of RSK2 into RSK2â/â MEFs restored A23187-induced morphological change, and decreased apoptosis, apoptotic DNA fragmentation and caspase-3 induction compared with RSK2â/â/mock MEFs. Taken together, our results demonstrated that RSK2 plays an important role in stress-tolerance and cell survival, resulting in cell proliferation and cancer development.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 440, Issue 1, 11 October 2013, Pages 112-118
Journal: Biochemical and Biophysical Research Communications - Volume 440, Issue 1, 11 October 2013, Pages 112-118
نویسندگان
Cheol-Jung Lee, Mee-Hyun Lee, Ji-Young Lee, Ji Hong Song, Hye Suk Lee, Yong-Yeon Cho,