Mini-reviewMenin interacting proteins as clues toward the understanding of multiple endocrine neoplasia type 1
Section snippets
MEN1, a complex genetic disease predisposing to endocrine tumors
Multiple Endocrine Neoplasia type 1 (MEN1, Online Mendelian Inheritance in Men (OMIM) 131100) is a cancer predisposition syndrome inherited as a dominant trait. It affects a variety of endocrine tissues, in particular parathyroids, endocrine pancreas, anterior pituitary, foregut-derived neuroendocrine tissues and adrenal cortex. Other tissues are affected in MEN1 patients, albeit less frequently: cutaneous proliferations such as angiofibroma, collagenoma, lipoma or melanoma, and peripheral or
Menin and the regulation of transcription
In the last 3 years, Menin has been shown to interact with several proteins of known function. It is striking that the first four protein partners (MIPs, for Menin Interacting Proteins) of Menin which have been unraveled are known for their central role in the regulation of transcription.
The prototype is JunD, a transcription factor belonging to the AP1 transcription complex family. Identified by the yeast two-hybrid method, the Menin–JunD interaction has been established by several other
Menin and intermediate filaments
Although Menin has been reported primarily as a nuclear protein [25], several reports have brought trustworthy indications that it may be present also in the cytoplasm [8], [26], [27]. However, there is, to our knowledge, no definite proof that a nuclear/cytoplasmic balance of Menin could be regulated during the cell cycle [27]. In this respect, it is striking that the protein glial fibrillary acidic protein (GFAP) has been recovered from a yeast two-hybrid screen of a human adult brain cDNA
Menin and the control of genome stability
The binding of Menin to Nm23H1 might be relevant also to the control of genomic stability as isoform 1 of the rat Nm23 (and not isoform 2) is associated to the centrosomes of interphase C6 glial cells [36]. The role of centrosomes in the maintenance of chromosome integrity is well documented, while they also orchestrate the formation of GFAP and Vimentin containing filaments through protein phosphorylations regulated by GTPases.
This is of particular interest since a role of Menin (either
Conclusion
Consistent with the fact that MEN1 represents a complex syndrome with –at the same time- a strict tissue specificity and a relatively broad spectrum of both associated tumors and phenotype expressivity, the presently known protein partners of Menin seem to drive it through various cellular compartments to act in different regulation pathways. In this respect, they have provided information that will turn out to be essential in the understanding of the pathogenicity of MEN1. However, at the
Acknowledgements
This article has been made possible after the June 2002 workshop on Multiple Endocrine Neoplasia organized in Grand Rapids, Mi, by Bin T. Teh. Our special tanks go to Anders Gobl and Naganari Ohkura who have made their results available to us prior to publication. A.P. is the recipient of an allocation de recherche from the French Ministry of Research and Technology, and B.Z. was supported by a stipend from CNRS. This work was funded by the Association pour la Recherche sur le Cancer (grant No.
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2022, Cellular and Molecular Gastroenterology and HepatologyCitation Excerpt :Similar to the previous observations in PNETs, Gfap and Men1 mRNA expression was significantly reduced in prolactinomas compared with WT pituitary (Figure 3, K). Because GFAP marks nestin+ subventricular neural stem cells34–36 and interacts with menin,37,38 we determined whether GFAP-negative GFAPΔMen1 pitNETs share features with neural stem cells by generating tumor neurosphere lines from multiple GFAPΔMen1 pituitary prolactinomas. Subsequent immunostaining of GFAPΔMen1 tumor neurospheres revealed that tumor cells co-expressed prolactin and the neural stem cell markers SOX2 and nestin, suggesting that the hormone-expressing tumor cells arose from a neural stem cell lineage (Figure 3, L).
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2015, International Journal of SurgeryCitation Excerpt :MEN-1 is caused by inactivating mutations of the MEN-1 gene on the long arm of chromosome 11 (11q13) [19]. This gene encodes for menin and is involved in regulation of cell growth, apoptosis and DNA repair [20]. The second most common endocrinopathy in MEN-1, after parathyroid tumor, are pNETs.
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