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

Yue Peng, Curtis Clark, Richard Luong, William H. Tu, Jane Lee, Daniel T. Johnson, Amrita Das, Thomas J. Carroll, Zijie Sun

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9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)40331-40342
Number of pages12
JournalJournal of Biological Chemistry
Volume286
Issue number46
DOIs
StatePublished - Nov 18 2011

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Peng, Y., Clark, C., Luong, R., Tu, W. H., Lee, J., Johnson, D. T., Das, A., Carroll, T. J., & Sun, Z. (2011). The leucine zipper putative tumor suppressor 2 protein LZTS2 regulates kidney development. Journal of Biological Chemistry, 286(46), 40331-40342. https://doi.org/10.1074/jbc.M111.302059