Menin: a scaffold protein that controls gene expression and cell signaling

•Molecular and structural basis for menin-mediated activation of gene transcription.•Multiple modes and molecular basis of menin-mediated suppression of gene transcription.•Menin regulates multiple cell signaling pathways.•Menin is regulated by multiple factors and signaling pathways.

The protein menin is encoded by the MEN1 gene, which is mutated in patients with multiple endocrine neoplasia type 1 (MEN1) syndrome. Although menin acts as a tumor suppressor in endocrine organs, it is required for leukemic transformation in mouse models. Menin possesses these dichotomous functions probably because it can both positively and negatively regulate gene expression, as well as interact with a multitude of proteins with diverse functions. Here, we review the recent progress in understanding the molecular mechanisms by which menin functions. The crystal structures of menin with different binding partners reveal that menin is a key scaffold protein that functionally crosstalks with various partners to regulate gene transcription and interplay with multiple signaling pathways.