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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor
07:16

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Published on: September 13, 2018

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

Yue Peng1, Curtis Clark, Richard Luong

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

The Journal of Biological Chemistry
|September 28, 2011
PubMed

Insights

Leucine zipper putative tumor suppressor 2 (LZTS2) is critical for kidney development. Loss of LZTS2 causes severe urinary tract defects by disrupting β-catenin signaling during nephrogenesis.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Leucine zipper putative tumor suppressor (LZTS) family proteins regulate transcription and cell cycle.
  • LZTS2 interacts with β-catenin and represses β-catenin-mediated transcription.

Purpose of the Study:

  • To investigate the biological role of LZTS2 in mammalian development.
  • To elucidate the function of LZTS2 in renal and urinary tract development using knockout mice.

Main Methods:

  • Generation and analysis of Lzts2 knockout (KO) mice.
  • Histological examination of embryonic kidneys and urinary tracts.
  • Analysis of β-catenin localization and Wnt signaling activity in Lzts2 null fibroblasts.

Main Results:

  • Lzts2 KO mice exhibited severe prenatal kidney and urinary tract malformations, including renal/ureteral duplication and hydronephrosis.
  • Ureteric bud outgrowth was altered in Lzts2 null embryos.
  • Loss of LZTS2 led to altered β-catenin subcellular localization and enhanced Wnt/β-catenin transcriptional activity in fibroblasts.

Conclusions:

  • LZTS2 plays a critical role in normal renal development.
  • LZTS2 functions as a regulator of the Wnt signaling pathway during nephrogenesis.
  • Disruption of LZTS2 impacts β-catenin-mediated processes essential for kidney formation.

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