Abstract

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 Ca²⁺-binding protein, and is sequestered in the cytosol at low glucose concentrations. Upon stimulation with glucose and activation of Ca²⁺ influx, or application of ATP as an intracellular Ca²⁺-mobilising agent, ChREBP rapidly translocates to the nucleus. In sorcin-silenced cells, ChREBP is constitutively present in the nucleus, and both glucose and Ca²⁺ are ineffective in stimulating further ChREBP nuclear shuttling. Whether an active Ca²⁺-sorcin element of ChREBP activation also exists in non-excitable cells is discussed.