Understanding HNF-1β through Identification of Interacting Proteins and Target Genes in the Kidney
type: CreativeWork
description: Hepatocyte nuclear factor-1Beta (HNF-1Beta) is a POU/homeodomain-containing transcription factor that regulates tissue-specific gene expression in the liver, kidney, pancreas, and other epithelial organs. During kidney development, HNF-1Beta is expressed in renal collecting ducts and all segments of the nephron. Mutation of HNF-1Beta causes maturity-onset diabetes of the young type 5 (MODY5) and kidney developmental anomalies including renal agenesis, hypoplasia, and cysts. Here, I studied interacting proteins and target genes to understand the function of HNF-1Beta in the kidney. Yeast two-hybrid screening was performed to identify binding partners of HNF-1Beta in the kidney. Zyxin and LPP were isolated as putative interacting proteins. The LIM-containing proteins, Zyxin and LPP, are focal adhesion proteins that shuttle between the cytoplasm and nucleus and play a role in the architectural organization of cells. Both Zyxin and LPP interact with HNF-1Beta and stimulate the transcriptional activity of HNF-1Beta in mIMCD3 renal epithelial cells. Epidermal growth factor (EGF), which plays a role in the progression of polycystic kidney disease, induces translocation of zyxin into the nucleus. These studies identify a novel pathway by which signals may be transmitted from the cell surface to regulate the activity of a nuclear transcription factor that is essential for epithelial differentiation in the kidney. Chromatin immunoprecipitaion and DNA chip analysis (ChIP-chip) were performed to identify direct target genes of HNF-1Beta in the kidney. Phosphodiesterase 4C (PDE4C) was identified as an HNF-1Beta target gene. PDE4C belongs to the phosphodiesterase superfamily of enzymes that control the intracellular concentration of cyclic adenosine monophosphate (cAMP) by catalyzing its hydrolysis. cAMP may play a role in cystogenesis by stimulating fluid secretion and cell proliferation. PDE4C is transcriptionally activated by HNF-1Beta and regulates cAMP levels in mIMCD3 renal…
abstract: Hepatocyte nuclear factor-1Beta (HNF-1Beta) is a POU/homeodomain-containing transcription factor that regulates tissue-specific gene expression in the liver, kidney, pancreas, and other epithelial organs. During kidney development, HNF-1Beta is expressed in renal collecting ducts and all segments of the nephron. Mutation of HNF-1Beta causes maturity-onset diabetes of the young type 5 (MODY5) and kidney developmental anomalies including renal agenesis, hypoplasia, and cysts. Here, I studied interacting proteins and target genes to understand the function of HNF-1Beta in the kidney. Yeast two-hybrid screening was performed to identify binding partners of HNF-1Beta in the kidney. Zyxin and LPP were isolated as putative interacting proteins. The LIM-containing proteins, Zyxin and LPP, are focal adhesion proteins that shuttle between the cytoplasm and nucleus and play a role in the architectural organization of cells. Both Zyxin and LPP interact with HNF-1Beta and stimulate the transcriptional activity of HNF-1Beta in mIMCD3 renal epithelial cells. Epidermal growth factor (EGF), which plays a role in the progression of polycystic kidney disease, induces translocation of zyxin into the nucleus. These studies identify a novel pathway by which signals may be transmitted from the cell surface to regulate the activity of a nuclear transcription factor that is essential for epithelial differentiation in the kidney. Chromatin immunoprecipitaion and DNA chip analysis (ChIP-chip) were performed to identify direct target genes of HNF-1Beta in the kidney. Phosphodiesterase 4C (PDE4C) was identified as an HNF-1Beta target gene. PDE4C belongs to the phosphodiesterase superfamily of enzymes that control the intracellular concentration of cyclic adenosine monophosphate (cAMP) by catalyzing its hydrolysis. cAMP may play a role in cystogenesis by stimulating fluid secretion and cell proliferation. PDE4C is transcriptionally activated by HNF-1Beta and regulates cAMP levels in mIMCD3 renal…
author: Choi, Yun-Hee
language: en
keywords: Cyclic AMP Receptor Protein, Polycystic Kidney Diseases, Hepatocyte Nuclear Factor 1-beta
date published: 2010-11-02T18:11:19Z
date modified: 2026-07-24T05:52:13Z
provider: University of Texas Southwestern Medical Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Texas Southwestern Medical Center

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2152.5/803