Posttranslational modification of catenin

The armadillo repeat domains of ß-catenin are essential for binding to its many partners including E-cadherin, a-catenin and TCF-4. This association of ß-catenin with various proteins is regulated by post-translational modification at specific sites of the arm repeats (Piedra et al., 2001). Sequences in central arm repeats 4-12 are required for ß-catenin to associate with E-cadherin (Hulsken et al., 1994). Moreover, phosphorylation of tyrosine residue 654 (located in arm repeat 12) decreases association of ß-catenin with E-cadherin (Roura et al., 1999). Simultaneously, phosphorylation of tyr-654 stimulates binding of ß-catenin to the basal transcription factor TATA-binding protein (TBP). Phosphorylation of tyr-654 removes steric hindrance at the C-terminal allowing better access of key components of the transcriptional machinery, such as TBP. Since Tcf-4 binds to armadillo repeats 3-8, its association with ß-catenin is not affected by phosphorylation of tyr-654 (arm repeat 12). ß-Catenin binding to a-catenin is determined by a short 31 amino-acid sequence in the first armadillo repeat of ß-catenin (Aberle et al., 1994). However, this association between ß- and a-catenin is not affected by any known post-translational modifications of tyrosine residues.

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