Menin molecular interactions: insights into normal functions and tumorigenesis.
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.
National Institute of Diabetes and Digestive and Kidney Diseases/NIH, 9000 Rockville Pike, Bethesda, MD 20892-1802, USA. SunitaA@intra.niddk.nih.gov
S K
SK
Agarwal
P A
PA
Kennedy
P C
PC
Scacheri
E A
EA
Novotny
A B
AB
Hickman
A
A
Cerrato
T S
TS
Rice
J B
JB
Moore
S
S
Rao
Y
Y
Ji
C
C
Mateo
S K
SK
Libutti
B
B
Oliver
S C
SC
Chandrasekharappa
A L
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Burns
F S
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Collins
A M
AM
Spiegel
S J
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Marx
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D003598:Cytoskeletal Proteins; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D004247:DNA