Fig. 8

CD133 regulates β-catenin signaling via its interaction with HDAC6. a CD133 regulates the formation of a tripartite complex involving HDAC6 and β-catenin, leading to the stabilization of the latter, which may then translocate to the nuclear compartment, where it activates the expression of genes, notably those associated with the Wnt/β-catenin pathway via its interaction with the TCF/LEF transcription factor. The interaction between CD133 and HDAC6 is mediated by IC1 and potentially lysine (K) 138 (numbered according to the splice variant s2). b Treatment of cells with tubacin, a specific inhibitor of HDAC6 deacetylase activity, leads to the degradation of acetylated β-catenin (Ac) and thus the impairment of transcriptional activity, while CD133 is endocytosed and degraded upon its transport to the endolysosomal compartment. Therefore, CD133/HDAC6/β-catenin interactions will have an impact on cancer cell proliferation and differentiation. Illustrations in panels a and b are adapted from Ref [362]