Division of Diabetes, Endocrinology and Metabolism, Section of Cell Biology, Department of Medicine, Imperial College London, SW7 2AZ London, UK.
J Endocrinol. 2012 May;213(2):115-22. doi: 10.1530/JOE-11-0480. Epub 2012 Mar 8.
Carbohydrate-responsive element binding protein (ChREBP (MLXIPL)) is emerging as an important mediator of glucotoxity both in the liver and in the pancreatic β-cells. Although the regulation of its nuclear translocation and transcriptional activation by glucose has been the subject of intensive research, it is still not fully understood. We have recently uncovered a novel mechanism in the excitable pancreatic β-cell where ChREBP interacts with sorcin, a penta-EF-hand Ca(2)(+)-binding protein, and is sequestered in the cytosol at low glucose concentrations. Upon stimulation with glucose and activation of Ca(2)(+) influx, or application of ATP as an intracellular Ca(2)(+)-mobilising agent, ChREBP rapidly translocates to the nucleus. In sorcin-silenced cells, ChREBP is constitutively present in the nucleus, and both glucose and Ca(2)(+) are ineffective in stimulating further ChREBP nuclear shuttling. Whether an active Ca(2)(+)-sorcin element of ChREBP activation also exists in non-excitable cells is discussed.
碳水化合物反应元件结合蛋白（ChREBP（MLXIPL））作为一种重要的葡萄糖毒性介质，在肝脏和胰腺β细胞中都有重要作用。尽管其核易位和转录激活的葡萄糖调节已经成为了研究的热点，但其机制仍未完全阐明。我们最近在兴奋的胰腺β细胞中发现了一种新的机制，ChREBP 与 sorcin（一种五 EF 手钙离子结合蛋白）相互作用，并在低葡萄糖浓度下被隔离在细胞质中。当受到葡萄糖刺激和钙离子内流激活，或应用作为细胞内钙离子动员剂的 ATP 时，ChREBP 迅速向核内易位。在沉默 sorcin 的细胞中，ChREBP 持续存在于核内，葡萄糖和钙离子都不能有效刺激 ChREBP 进一步核转位。在非兴奋细胞中是否存在 ChREBP 激活的活性钙离子-sorcin 元件也在讨论之中。
