Kaiso/p120-Catenin and TCF/β-Catenin Complexes Coordinately Regulate Canonical Wnt Gene Targets

Abstract

Beta-catenin-dependent or canonical Wnt signals are fundamental in animal development and tumor progression. Using Xenopus laevis, we report that the BTB/POZ zinc finger family member Kaiso directly represses canonical Wnt gene targets (Siamois, c-Fos, Cyclin-D1, and c-Myc) in conjunction with TCF/LEF (TCF). Analogous to beta-catenin relief of TCF repressive activity, we show that p120-catenin relieves Kaiso-mediated repression of Siamois. Furthermore, Kaiso and TCF coassociate, and combined Kaiso and TCF derepression results in pronounced Siamois expression and increased beta-catenin coprecipitation with the Siamois promoter. The functional interdependency is underlined by Kaiso suppression of beta-catenin-induced axis duplication and by TCF-3 rescue of Kaiso depletion phenotypes. These studies point to convergence of parallel p120-catenin/Kaiso and beta-catenin/TCF signaling pathways to regulate gene expression in vertebrate development and possibly carcinogenesis.

A feedback loop that regulates the expression of polycomb group protein Suz12 via non-canonical WNT signaling pathway in blast crisis of chronic myeloid leukemia

“…From our point of view, it suggests that Wnt5a and Wnt11 should be increased in the context of patients who enter that stage of the disease and always results in a worsening of their clinical condition. On the other hand, Wnt11 is one of several β-catenin/ TCF target genes that also contain a putative Kaiso-binding site in its promoter region, suggesting that Kaiso and TCF/ LEF cooperate to repress Wnt11 transcription [14] (Figure 2c). Besides, the present research has shown that knock-down of Suz12 by small interfering RNA (siRNA) produces a significant decrease of 98% in the expression of Kaiso in K562 cells, the first established human immortalized myelogenous leukemia line [13].…”

Collagen 11a1 is indirectly activated by lymphocyte enhancer-binding factor 1 (Lef1) and negatively regulates osteoblast maturation

“…One footprint was determined to be a binding site for a zinc-finger protein that was termed FP9C (Kinoshita et al, 1997). The only reported zinc-finger protein to interact with Tcf/Lef1 is Kaiso, which competes with β-catenin for binding to Tcf-3 resulting in transcriptional repression of the Samois gene in X. laevis (Park et al, 2005). This is unlikely to be the factor through which Lef1 activates the Col11a1 promoter for several reasons.…”

“…2 and 3). Finally, Kaiso is reported to be a repressor of transcription so interaction between Lef1 and Kaiso is unlikely to result in transcriptional activation (Kim et al, 2004;Park et al, 2005;Spring et al, 2005).…”

Transgenic Wnt/TCF pathway reporters: all you need is Lef?

“…This 'default repression' (Barolo and Posakony, 2002) has been demonstrated to be critical for the proper regulation of many Wnt target genes. In some cases, default repression by TCFs appears to be at least as important as Wnt/TCFmediated activation for proper target gene regulation (e.g., Brannon et al, 1997;Crawford et al, 1999;Yang et al, 2000;Knirr and Frasch, 2001;Merrill et al, 2001;Park et al, 2005). It is quite possible that Wnt signaling events that direct the de-repression of TCF target genes, but that do not trigger robust activation by TCFs, might not be detectable by multimerized TCF reporters, which have a baseline of zero and thus cannot register changes in repression (Merrill et al, 2004).…”