NEMO stabilizes c‐Myc through direct interaction in the nucleus

Abstract The transcription factor c-Myc is a cellular oncoprotein generally upregulated in most of human cancers. NF-κB essential modulator (NEMO) caused phosphorylation and stabilization of c-Myc protein in the nucleus through direct interaction. The interaction caused reduced ubiquitination of c-Myc by inhibiting ubiquitinating activity of Fbw7 without blocking the interaction between c-Myc and Fbw7. As a consequence, NEMO enhanced the expression of several selected c-Myc targets. Compared to the classical role as an essential subunit for the activity of IKK complex, stabilization of c-Myc by direct interaction is a unique function of NEMO, representing a new mechanism to regulate c-Myc activity. Structured summary MINT- 8045088 : c-Myc (uniprotkb: P01106 ) and NEMO (uniprotkb: Q9Y6K9 ) colocalize (MI: 0403 ) by fluorescence microscopy (MI: 0416 ) MINT- 8045072 , MINT- 8045101 : c-Myc (uniprotkb: P01106 ) physically interacts (MI: 0915 ) with NEMO (uniprotkb: Q9Y6K9 ) by anti tag coimmunoprecipitation (MI: 0007 )