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193

To arrest or not: a question of health or disease

Gang Pei
（Tongji University, China）

The cellular network of signal transduction, comprised of hundreds of distinct but cross-linked pathways that provide diversity and plasticity of cell functions, has to be delicately regulated. It seems there are a few multifunctional regulators which play important roles in maintaining the integrity of the network, and β-arrestin appears to be one of them.

The classical paradigm of β-arrestin function is to arrest the activated G-protein-coupled receptors, but recent evidence indicates that it also desensitizes other signal cascades. For example, our study reveals that β-arrestin tightly regulates all three major NF-kB pathways through different mechanisms, and disruption of this regulation leads to aberrant NF-kB activation and robust upregulation of infl ammatory cytokines.

Interestingly, in addition to its well-established negative regulatory functions, β-arrestin also facilitates the formation of functional signaling complexes. For instance, β-arrestin 1 can locate to the nucleus and complex with the histone acetyltransferase p300 to epigenetically modulate gene expression. Up-regulation of β-arrestin 1 expression significantly increases disease severity in a mouse model of multiple sclerosis. By contrast, β-arrestin 2 is located abundantly in the cytoplasm, and functionally scaffolds Akt and Src to the activated insulin receptor in mediation of insulin signaling, and its dysfunction contributes to insulin resistance and type II diabetes.

Therefore, to arrest or not, as regulated by β-arrestin, is a key question in signal transduction, and could critically determine the status of health or disease.

编辑: ludongcn    作者:丁香园通讯员