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

Research output: Contribution to journalArticlepeer-review

10 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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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