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J Biol Chem. 2011 Nov 18;286(46):40331-42. doi: 10.1074/jbc.M111.302059. Epub 2011 Sep 26.

The leucine zipper putative tumor suppressor 2 protein LZTS2 regulates kidney development.

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  • 1Department of Urology, Stanford University School of Medicine, Stanford, California 94305-5328, USA.

Abstract

Members of the leucine zipper putative tumor suppressor (LZTS) family play crucial roles in transcription modulation and cell cycle control. We previously demonstrated that LZTS2 functions as a novel β-catenin-interacting protein and represses β-catenin-mediated transcription on T-cell factor/lymphoid enhancing factor. Here, we investigate the biological role of LZTS2 using newly established Lzts2 KO mice. Homozygosity for loss-of-function of the Lzts2-targeted allele resulted in severe kidney and urinary tract developmental defects, including renal/ureteral duplication, hydroureter, and hydronephrosis, which were visible prenatally. Altered ureteric bud outgrowth was identified in Lzts2 null embryos. Further analysis indicated that β-catenin subcellular localization was altered in fibroblasts isolated from Lzts2 null embryos. In addition, Wnt growth factor-induced β-catenin-mediated transcriptional activity was increased in Lzts2 null fibroblasts, suggesting a direct role for Lzts2 in the Wnt signaling pathway. These data demonstrate a critical role of LZTS2 in renal development and implicate LZTS2 as a critical regulator of β-catenin-mediated nephrogenesis.

PMID:
21949185
[PubMed - indexed for MEDLINE]
PMCID:
PMC3220563
Free PMC Article

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