This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Cao, Y.
Right arrow Articles by Ning, G.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cao, Y.
Right arrow Articles by Ning, G.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2009, p. 5477-5487, Vol. 29, No. 20
0270-7306/09/$08.00+0     doi:10.1128/MCB.00335-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Nuclear-Cytoplasmic Shuttling of Menin Regulates Nuclear Translocation of β-Catenin{triangledown}

Yanan Cao,1,{dagger} Ruixin Liu,1,{dagger} Xiuli Jiang,1 Jieli Lu,1 Jingjing Jiang,1 Changxian Zhang,3 Xiaoying Li,1,4* and Guang Ning1,2*

Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism and Chinese-French Laboratory of Genomics and Life Sciences, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China,1 Laboratory for Endocrine and Metabolic Diseases, Institute of Health Sciences, SIBS, Chinese Academy of Sciences, China,2 Laboratoire Genetique et Cancer, CNRS, UMR5201, Faculte de Medecine Univ-Lyon1, 69008 Lyon, France,3 Shanghai Key Laboratory for Endocrine Tumors, E-Institute of Shanghai Universities, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China4

Received 16 March 2009/ Returned for modification 8 April 2009/ Accepted 8 July 2009

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.

* Corresponding author. Mailing address: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China. Phone: 86 21 64370045. Fax: 86 21 64373514. E-mail for Xiaoying Li: lixy{at}sibs.ac.cn. E-mail for Guang Ning: guangning{at}medmail.com.cn

{triangledown} Published ahead of print on 3 August 2009.

{dagger} These authors contributed equally to this work.

Molecular and Cellular Biology, October 2009, p. 5477-5487, Vol. 29, No. 20
0270-7306/09/$08.00+0     doi:10.1128/MCB.00335-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»