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

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.

Pubmed ID: 21949185


  • Peng Y
  • Clark C
  • Luong R
  • Tu WH
  • Lee J
  • Johnson DT
  • Das A
  • Carroll TJ
  • Sun Z


The Journal of biological chemistry

Publication Data

November 18, 2011

Associated Grants

  • Agency: NCI NIH HHS, Id: R01 CA070297
  • Agency: NCI NIH HHS, Id: R01 CA151623

Mesh Terms

  • Animals
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Embryo, Mammalian
  • Kidney
  • Mice
  • Mice, Knockout
  • Organogenesis
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • Wnt Proteins
  • Wnt Signaling Pathway
  • beta Catenin