Bauer et al. have identified and characterized a protein, termed Reptin52 that associates with Pontin52, which positively regulates β-catenin-mediated transcription in the Wnt pathway. Reptin52 and Pontin52 exhibited homo- and heterotypic association, as assayed by immunoprecipitation. Furthermore, Reptin52 associated with β-catenin and the TATA-box binding protein (TBP). Precipitation assays performed using truncated β-catenin mutants demonstrated that Pontin52 and Reptin52 bind the same site on β-catenin. Overexpression of Reptin52 strongly inhibited transcription of a reporter gene by the β-catenin-TCF4 (T-cell factor 4) complex, even in the presence of Pontin52, which may suggest that Reptin52 has greater affinity than Pontin52 for β-catenin. Genetic experiments in Drosophila mutants revealed that drep or dpon null mutants were lethal; however, conditional mutation crosses demonstrated that for wing formation dPon functions as a positive regulator of Wg (Wnt) signaling, whereas dRep represses Wg signaling. Thus, another level of complexity has been uncovered in Wnt signal control, and the authors suggest that the ability of Pontin52 and Reptin52 to homo- and hetero-oligomerize might allow for incremental changes in β-catenin-TCF4-mediated transcription.
Bauer, A., Chauvet, S., Huber, O., Usseglio, F., Rothbächer, U., Aragnol, D., Kemler, R., and Pradel, J. (2000) Pontin52 and Reptin52 function as antagonistic regulators of β-catenin signaling activity. EMBO J. 19: 6121-6130. [Abstract] [Full Text]