Analysis of Wnt signal transduction via cAMP responsive element

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MITF is a transcription factor containing a basic helix-loop-helix leucine-zipper motif. MITE consists of many isoforms with different N-termini, termed MITF-M,MITE-A,MITF-H, and MITF-D etc. MITF-M is indispensable for melanocyte differentiation.We showed that Wnt signaling activates the melanocyte-specific gene DOPAchrome tautomerase (DCT) and MITF-M. Further MITF-M efficiently activates the transcription of DCT and its own MITF-M gene by interaction with a nuclear mediator of Wnt signaling, LEE-1. Interestingly, MITF-M can function as a non-DNA-binding coactivator for LEF-1. MITE-A,MITF-H, and MITF-D also contain its coactivator function as MITF-M does.DCT gene activation by Wnt signaling is required for cAMP responsive elements (CRE)-like sequence TGAGGTCA in the DCT gene promoter. It is suggested that the TGAGGTCA does not bind CREB, but does a certain nuclear receptor.On the contrary, DCT is specifically expressed in retinal pigment epithelium (RPE) as well as in melanocytes. We have found that OTX2, a homeodomain-containing transcription factor, interacts with MITE, thereby regulating the expression of melanin-synthesis enzymes such as tyrosinase and DOT.Moreover, we examined the expression of MITE in cells where Wnt signaling may be involved in development and homeostasis. We thus found that MITE is expressed in the germ cells of mouse testis.