direct interaction of menin leads to ubiquitinproteasomal degradation of catenin menin encoded by the multiple endocrine neoplasia type 1 men1 gene is a tumor suppressor and transcription regulator menin interacts with various proteins as a scaffold protein and is proposed to play important roles in multiple physiological and pathological processes by controlling gene expression proliferation and apoptosis the mechanisms underlying menins suppression of tumorigenesis are largely elusive in this study we showed that menin was essential for the regulation of canonical wntcatenin signaling in cultured cells the cterminal domain of menin was able to directly interact with and promote ubiquitinmediated degradation of catenin we further revealed that overexpression of menin downregulated the transcriptional activity of catenin and target gene expression moreover menin efficiently inhibited catenin protein levels transcriptional activity and proliferation of human renal carcinoma cells with an activated catenin pathway taken together our results provide novel molecular insights into the tumor suppressor activity of menin which is partly mediated by proteasomal degradation of catenin and inhibition of wntcatenin signaling