PMID:24174533

Citation	Lee, SH, Zhu, C, Peng, Y, Johnson, DT, Lehmann, L and Sun, Z' (2013) Identification of A Novel Role of ZMIZ2 in Regulating the Activity of the Wnt/β-catenin Signaling Pathway. J. Biol. Chem. '
Abstract	ZMIZ2, also named ZIMP7, is a PIAS-like protein and a transcriptional co-activator. In this study, we investigated the interaction between ZMIZ2 and β-catenin, a key regulator of the Wnt signaling pathway. We demonstrated that the expression of exogenous ZMIZ2 augments TCF (T cell factor) and β-catenin mediated transcription. In contrast, shRNA knockdown of ZMIZ2 expression specifically represses the enhancement of TCF/β-catenin mediated transcription by ZMIZ2. Using Wnt3a conditioned media (Wnt3a-CM), we demonstrated that ZMIZ2 can enhance Wnt ligand induced TCF/β-catenin mediated transcription. We also showed a promotional role of ZMIZ2 in enhancing β-catenin downstream target gene expression in human cells and in Zmiz2 null (Zmiz2-/-) mouse embryonic fibroblasts (MEFs). The regulatory role of Zmiz2 in Wnt induced TCF/β-catenin mediated transcription can be restored in Zmiz2-/- MEFs that were infected with adenoviral expression vectors for Zmiz2. Moreover, enhancement of Zmiz2 on TCF/β-catenin mediated transcription was further demonstrated in Zmiz2 knockout and Axin2 reporter compound mice. Furthermore, the protein-protein interaction between ZMIZ2 and β-catenin was identified by co-immunoprecipitation and in vitro protein pulldown assays. We also observed recruitment of endogenous ZMIZ2 onto the promoter region of the Axin 2 gene, a β-catenin downstream target promoter, in a Wnt ligand inducible manner. Finally, a promotional role of ZMIZ2 on cell growth was demonstrated in human cell lines and Zmiz2 knockout MEFs. Our findings demonstrate a novel interaction between ZMIZ2 and β-catenin, and elucidate a novel mechanism for PIAS like proteins in regulating Wnt signaling pathways.
Links	PubMed Online version:10.1074/jbc.M113.529727
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:A3KMG8		GO:0010468: regulation of gene expression	ECO:0000314:		P		Figure 2 shows the effects of ZMIZ2 on the Cyclin D1-promoter in HEK29 in media containing various shRNA constructs. Promoter activity was observed by measuring the luciferase and B-gal activities of the cells.	complete CACAO 9023

References

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