کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10750075 | 1050296 | 2015 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
SHC1 sensitizes cancer cells to the 8-Cl-cAMP treatment
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کلمات کلیدی
AMPKHDFpKaHFFSH2SHC1AMP-activated protein kinase - AMP-پروتئین کیناز فعال شده استp38 MAP kinase - p38 mAP kinasep38 MAPK - P38 MAPKCancer therapy - سرطان درمانHuman dermal fibroblasts - فیبروبلاست های پوستی انسانhuman foreskin fibroblasts - فیبروبلاستهای مزرعه انسانی انسانSrc Homology 2 - همبستگی Src 2p38 mitogen-activated protein kinase - پروتئین کیناز متیوژن فعال p38Cyclic AMP-dependent protein kinase - پروتئین کیناز وابسته به AMP
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
8-Chloro-cyclic AMP (8-Cl-cAMP) is a cyclic AMP analog that induces growth inhibition and apoptosis in a broad spectrum of cancer cells. Previously, we found that 8-Cl-cAMP-induced growth inhibition is mediated by AMP-activated protein kinase (AMPK) as well as p38 mitogen-activated protein kinase (p38 MAPK). To identify downstream mediators of the 8-Cl-cAMP signaling, we performed co-immunoprecipitation combined with mass spectrometry using the anti-AMPK or p38 MAPK antibodies. Through this approach, SHC1 was identified as one of the binding partners of p38 MAPK. SHC1 phosphorylation was suppressed by 8-Cl-cAMP in HeLa and MCF7 cancer cells, which was mediated by its metabolites, 8-Cl-adenosine and 8-Cl-ATP; however, 8-Cl-cAMP showed no effect on SHC1 phosphorylation in normal human fibroblasts. SHC1 siRNA induced AMPK and p38 MAPK phosphorylation and growth inhibition in cancer cells, and SHC1 overexpression re-sensitized human foreskin fibroblasts to the 8-Cl-cAMP treatment. SHC1 phosphorylation was unaffected by Compound C (an AMPK inhibitor) and SB203580 (a p38 MAPK inhibitor), which suggests that SHC1 is upstream of AMPK and p38 MAPK in the 8-Cl-cAMP-stimulated signaling cascade. On the basis of these findings, we conclude that SHC1 functions as a sensor during the 8-Cl-cAMP-induced growth inhibition in SHC1-overexpressing cancer cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 463, Issue 4, 7 August 2015, Pages 673-678
Journal: Biochemical and Biophysical Research Communications - Volume 463, Issue 4, 7 August 2015, Pages 673-678
نویسندگان
Ki Young Choi, Young Jun Cho, Jeong Seon Kim, Young-Ho Ahn, Seung Hwan Hong,