کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1960351 1057957 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Akt versus p53 in a Network of Oncogenes and Tumor Suppressor Genes Regulating Cell Survival and Death
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Akt versus p53 in a Network of Oncogenes and Tumor Suppressor Genes Regulating Cell Survival and Death
چکیده انگلیسی

The tumor suppressor protein, p53, and the oncoprotein, Akt, are involved in a cross talk that could be at the core of a cell’s control machinery for switching between survival and death. This cross talk is a combination of reciprocally antagonistic pathways emanating from p53 and Akt, and also involves another tumor suppressor gene, PTEN, and another oncogene, Mdm2; such a connected network of cancer-relevant genes must be significant and demands a critical study. The p53-Akt network is shown in this report to possess the potential to exhibit bistability, a phenomenon in which two stable steady states of the system coexist for a fixed set of control parameter values. A hierarchy of qualitative networks and abstract kinetic models are analyzed and simulated on a computer to demonstrate the robustness of the bistable behavior, which, as argued in this study, is a likely candidate mechanism for a cellular survival-death switch. The analysis applies to cells that are neither p53-null nor Akt-null. The models presented here offer experimental predictions on the identity of control parameters of apoptotic thresholds and on network perturbations (including DNA damage and Akt inhibition) that are sufficient to generate switching between pro-survival and pro-death cellular states.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 91, Issue 3, 1 August 2006, Pages 857–865
نویسندگان
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