{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/803"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/803","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Understanding HNF-1β through Identification of Interacting Proteins and Target Genes in the Kidney","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 epithelial cells. Antibody staining showed that PDE4C is localized in the primary cilium and there interacts with a protein complex containing AKAP150, adenylyl cyclase 5/6 (AC5/6), protein kinase A (PKA), and polycystin-2 (PKD2). These results identify a cAMP-regulating protein complex that is localized in the primary cilium and is disrupted in PKD.","abstract_html":"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 epithelial cells. Antibody staining showed that PDE4C is localized in the primary cilium and there interacts with a protein complex containing AKAP150, adenylyl cyclase 5/6 (AC5/6), protein kinase A (PKA), and polycystin-2 (PKD2). These results identify a cAMP-regulating protein complex that is localized in the primary cilium and is disrupted in PKD.","abstract_has_math":false,"creators":["Choi, Yun-Hee"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Igarashi, Peter"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-11-02T18:11:19Z","date_published":"2010-11-02T18:11:19Z","updated_at":"2026-07-24T05:52:13Z","subjects":["Cyclic AMP Receptor Protein","Polycystic Kidney Diseases","Hepatocyte Nuclear Factor 1-beta"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["743217936"],"render_values":[{"text":"743217936","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/803","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Igarashi, Peter"]},{"key":"dc:creator","label":"Author","values":["Choi, Yun-Hee"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2010-11-02T18:11:19Z","2010-11-02"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","Text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Cyclic AMP Receptor Protein","Polycystic Kidney Diseases","Hepatocyte Nuclear Factor 1-beta"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/803","743217936"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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 epithelial cells. Antibody staining showed that PDE4C is localized in the primary cilium and there interacts with a protein complex containing AKAP150, adenylyl cyclase 5/6 (AC5/6), protein kinase A (PKA), and polycystin-2 (PKD2). These results identify a cAMP-regulating protein complex that is localized in the primary cilium and is disrupted in PKD."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Understanding HNF-1β through Identification of Interacting Proteins and Target Genes in the Kidney"]}]}],"canonical_facts":{"dc:contributor":["Igarashi, Peter"],"dc:creator":["Choi, Yun-Hee"],"dc:date":["2010-11-02T18:11:19Z","2010-11-02"],"dc: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 epithelial cells. Antibody staining showed that PDE4C is localized in the primary cilium and there interacts with a protein complex containing AKAP150, adenylyl cyclase 5/6 (AC5/6), protein kinase A (PKA), and polycystin-2 (PKD2). These results identify a cAMP-regulating protein complex that is localized in the primary cilium and is disrupted in PKD."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/803","743217936"],"dc:language":["en"],"dc:subject":["Cyclic AMP Receptor Protein","Polycystic Kidney Diseases","Hepatocyte Nuclear Factor 1-beta"],"dc:title":["Understanding HNF-1β through Identification of Interacting Proteins and Target Genes in the Kidney"],"dc:type":["Thesis","Text"]},"updated_at":"2026-07-24T05:52:13Z"}