Nuclear-cytoplasmic shuttling of menin regulates nuclear translocation of {beta}-catenin.
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 beta cells. We have found that menin contains two functional nuclear export signals and that there is nuclear accumulation of beta-catenin in Men1-null mouse embryonic fibroblasts and insulinoma tissues from beta-cell-specific Men1 knockout mice. It is reported that the deregulation of Wnt/beta-catenin signaling caused by inactivation of tumor suppressors results in abnormal development or tumorigenesis. We further revealed that overexpression of menin reduces beta-catenin nuclear accumulation and its transcriptional activity. Menin is able to directly interact with beta-catenin and carry beta-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/beta-catenin signaling.
Cao
Yanan
Y
Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
Liu
Ruixin
R
Jiang
Xiuli
X
Lu
Jieli
J
Jiang
Jingjing
J
Zhang
Changxian
C
Li
Xiaoying
X
Ning
Guang
G
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
C484898:Men1 protein, mouse; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D051176:beta Catenin