Positional Cloning of MEN1 Gene

Chandrasekharappa, S C.

Abstract

We have shown that inherited mutations in the MEN1 gene predispose individuals to develop multiple endocrine neoplasia type 1 (MEN1), characterized by multiple tumors of the parathyroid, gastrointestinal (GI) endocrine, and anterior pituitary tissues. We have shown that the MEN1 encoded protein (menin) is located primarily in the nucleus, and it interacts with JunD, a member of the AP1 family transcription factors. The menin-JunD interaction results in the repression of JunD- induced transcription, and the protein domains involved in their interaction have been identified. Also, potential interactions of menin with other cellular proteins are being investigated by the yeast two- hybrid system, co-immunoprecipitation and GST?menin pull-down assays. MEN1 homologous genes from mouse, zebrafish and Drosophila have been identified. In order to understand the functional role of menin, a mouse knockout model is being generated by homologous recombination, using the cre-lox system to allow tissue specific inactivation. - Cancer Research

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Human Genome Research Institute (NHGRI)
• Type: Intramural Research (Z01)
• Project #: 1Z01HG000029-05
• Application #: 6290274
• Study Section: Special Emphasis Panel (GMBB)
• Support Year: 5
• Fiscal Year: 1999

Institution

• Name: National Human Genome Research Institute
• Country: United States

Publications

Rodriguez, Virginia; Chen, Yidong; Elkahloun, Abdel et al. (2007) Chromosome 8 BAC array comparative genomic hybridization and expression analysis identify amplification and overexpression of TRMT12 in breast cancer. Genes Chromosomes Cancer 46:694-707

Ozawa, Atsushi; Agarwal, Sunita K; Mateo, Carmen M et al. (2007) The parathyroid/pituitary variant of multiple endocrine neoplasia type 1 usually has causes other than p27Kip1 mutations. J Clin Endocrinol Metab 92:1948-51

Ji, Youngmi; Prasad, Nijaguna B; Novotny, Elizabeth A et al. (2007) Mouse embryo fibroblasts lacking the tumor suppressor menin show altered expression of extracellular matrix protein genes. Mol Cancer Res 5:1041-51

Sun, Mei; Srikantan, Vasantha; Ma, Lanfeng et al. (2006) Characterization of frequently deleted 6q locus in prostate cancer. DNA Cell Biol 25:597-607

Sood, Raman; English, Milton A; Jones, MaryPat et al. (2006) Methods for reverse genetic screening in zebrafish by resequencing and TILLING. Methods 39:220-7

Scacheri, Peter C; Davis, Sean; Odom, Duncan T et al. (2006) Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis. PLoS Genet 2:e51

Cerrato, Aniello; Parisi, Michael; Santa Anna, Sonia et al. (2006) Genetic interactions between Drosophila melanogaster menin and Jun/Fos. Dev Biol 298:59-70

Agarwal, S K; Kennedy, P A; Scacheri, P C et al. (2005) Menin molecular interactions: insights into normal functions and tumorigenesis. Horm Metab Res 37:369-74

Zainabadi, Kayvan; Benyamini, Payam; Chakrabarti, Rita et al. (2005) A 700-kb physical and transcription map of the cervical cancer tumor suppressor gene locus on chromosome 11q13. Genomics 85:704-14

Agarwal, Sunita K; Lee Burns, A; Sukhodolets, Karen E et al. (2004) Molecular pathology of the MEN1 gene. Ann N Y Acad Sci 1014:189-98