TI - The Axin1 scaffold protein promotes formation of a degradation complex for c-Myc . AB - Expression of the c-Myc proto-oncoprotein is tightly regulated in normal cells . Phosphorylation at two conserved residues , threonine58 ( T58 ) and serine62 ( S62 ) , regulates c-Myc protein stability . In cancer cells , c-Myc can become aberrantly stabilized associated with altered T58 and S62 phosphorylation . A complex signalling cascade involving GSK3beta kinase , the Pin1 prolyl isomerase , and the PP2A-B56alpha phosphatase controls phosphorylation at these sites . We report here a novel role for the tumour suppressor scaffold protein Axin1 in facilitating the formation of a degradation complex for c-Myc containing GSK3beta , Pin1 , and PP2A-B56alpha . Although knockdown of Axin1 decreases the association of c-Myc with these proteins , reduces T58 and enhances S62 phosphorylation , and increases c-Myc stability , acute expression of Axin1 reduces c-Myc levels and suppresses c-Myc transcriptional activity . Moreover , the regulation of c-Myc by Axin1 is impaired in several tested cancer cell lines with known stabilization of c-Myc or loss of Axin1 . This study provides critical insight into the regulation of c-Myc expression , how this can be disrupted in three cancer types , and adds to our knowledge of the tumour suppressor activity of Axin1 .