The energy sensing LKB1–AMPK pathway regulates p27kip1 phosphorylation mediating the decision to enter autophagy or apoptosis
The energy sensing LKB1–AMPK pathway regulates p27kip1 phosphorylation mediating the decision to enter autophagy or apoptosis
Nature cell biology, February 2007
Speaker：傅孝瑜 Time: 2007/05/30 14:10~15:00
Commentator：林以行 老師 Place: Room601
Abstract：
Sufficient nutrients and proper growth signaling are essential for cell proliferation and survival. Through the receptor tyrosine kinase(RTK) on the cell membrane, growth factor activates the phosphatidylinositol 3 kinase (PI(3)K) pathway(1). At the downstream of this pathway, Akt inhibits cyclin-dependent kinase inhibitor p27Kip1 (inhibits the kinase activity of cyclin E-cdk2, resulting in cell-cycle arrest at G1 phase) and promotes cell cycle progression. However, previous studies mentioned that p27 also regulates motility and cell survival, suggesting that its role extends beyond cell-cycle regulation (2). Under metabolic stress, decline in ATP:ADP ratios results in accumulation of AMP, which activates AMPK and the Peutz-Jeghers syndrome gene product LKB1, functions as an intracellular energy sensor regulating metabolism and cell proliferation. In this paper, the authors indicated that during metabolic stress Thr 198 phosphorylation promotes p27 stability(3), and stable p27 accumulation is a determinant of whether quiescent cells enter the autophagy cell survival pathway or undergo rapid cell death by apoptosis. Furthermore, they linked the regulation of p27 to the nutrient-sensing AMPK-LKB1 pathway. It may be the cause how tumor cell overcome decreased blood supply during tumorigenesis.
Reference：
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