title: The leucine zipper putative tumor suppressor 2 protein LZTS2 regulates kidney development.
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.
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, California 94305-5328, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Peng
authors.forename: Curtis
authors.initials: C
authors.lastname: Clark
authors.forename: Richard
authors.initials: R
authors.lastname: Luong
authors.forename: William H
authors.initials: WH
authors.lastname: Tu
authors.forename: Jane
authors.initials: J
authors.lastname: Lee
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Johnson
authors.forename: Amrita
authors.initials: A
authors.lastname: Das
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Carroll
authors.forename: Zijie
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000196:embryology*; D007668:Kidney / Q000002:abnormalities / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D038081:Organogenesis / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C569000:LZTS2 protein, mouse; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin