Menin molecular interactions: insights into normal functions and tumorigenesis

SK Agarwal, PA Kennedy, PC Scacheri… - Hormone and …, 2005 - thieme-connect.com
SK Agarwal, PA Kennedy, PC Scacheri, EA Novotny, AB Hickman, A Cerrato, TS Rice…
Hormone and Metabolic Research, 2005thieme-connect.com
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease predisposed
by heterozygous germline mutations in the MEN1 tumor suppressor gene. Biallelic loss of
MEN1 resulting from small mutation and/or loss of heterozygosity occurs in a large tissue
spectrum of MEN1 tumors or non-hereditary tumors. Mouse models of MEN1
underexpression or overexpression have also supported the tumor-suppressor effect of the
MEN1 gene. Menin, the 610-amino-acid protein encoded by MEN1, is expressed …
Abstract
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease predisposed by heterozygous germline mutations in the MEN1 tumor suppressor gene. Biallelic loss of MEN1 resulting from small mutation and/or loss of heterozygosity occurs in a large tissue spectrum of MEN1 tumors or non-hereditary tumors. Mouse models of MEN1 underexpression or overexpression have also supported the tumor-suppressor effect of the MEN1 gene. Menin, the 610-amino-acid protein encoded by MEN1, is expressed ubiquitously and found predominantly in the nucleus. Sequence analyses do not reveal motifs of known function other than two nuclear localization sequences. Menin has been found to partner in vitro with a variety of proteins that comprise transcription factors, DNA processing factors, DNA repair proteins, and cytoskeletal proteins. The diverse functions of menin interactors suggest roles for menin in multiple biological pathways. Inactivation of menin switches its JunD partner from a downstream action of growth suppression to growth promotion. This is a plausible mechanism for menin tumorigenesis.
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