Nuclear-Cytoplasmic Shuttling of Menin Regulates Nuclear Translocation of β-Catenin

Abstract

Menin, which is encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor suppressor and transcriptional regulator. Menin controls proliferation and apoptosis of cells, especially pancreatic β cells. We have found that menin contains two functional nuclear export signals and that there is nuclear accumulation of β-catenin in Men1-null mouse embryonic fibroblasts and insulinoma tissues from β-cell-specific Men1 knockout mice. It is reported that the deregulation of Wnt/β-catenin signaling caused by inactivation of tumor suppressors results in abnormal development or tumorigenesis. We further revealed that overexpression of menin reduces β-catenin nuclear accumulation and its transcriptional activity. Menin is able to directly interact with β-catenin and carry β-catenin out of the nucleus via nuclear-cytoplasmic shuttling in a CRM1-dependent manner. These results imply that menin may control cell proliferation through suppression of Wnt/β-catenin signaling.

ACKNOWLEDGMENTS

This research is supported by grants from the Shanghai Education Commission (Y0204), Shanghai Committee of Science and Technology (08DZ2271000), Natural Science Foundation of China (08410706700, 30725037, and 30890043), and 973 project (2006CB503904).

We declare that there is no conflict of interest that would prejudice the impartiality of this scientific work.