Chimeric proteins comprising liver enriched transcription factors and nucleic acids encoding the same

US6025196A · kind A · utility

Assignee

• The Rockefeller University · US

Inventors

• Frances M. Sladek · Riverside, US
• Weimin Zhong · New York, US
• James E. Darnell, Jr. · Larchmont, US

Key dates

• Filing date: Mar 11, 1998
• Grant date: Feb 15, 2000
• Expiry date: Mar 11, 2018

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/81
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

HNF-4 (hepatocyte nuclear factor 4) is a protein enriched in liver extracts that binds to sites required for the transcription of the transthyretin (TTR) and apolipoprotein CIII (apoCIII) genes (Costa et al., 1989; Costa et al., 1990; Leff et al., 1989). We have purified HNF-4 protein (54 kD) and isolated a cDNA clone encoding the protein. HNF-4 is a member of the steroid hormone receptor superfamily with an unusual amino acid in the conserved "knuckle" of the first zinc finger (DGCKG). This and the fact that HNF-4 does not bind significantly to estrogen, thyroid hormone or glucocorticoid response elements indicate that HNF-4 may represent a new subfamily. HNF-4 binds to its recognition site as a dimer and activates transcription in a sequence-specific fashion in nonhepatic (HeLa) cells. HNF-4 mRNA is present in kidney and intestine as well as liver but is absent in other tissues. DNA binding data suggest that HNF-4 could be identical to liver factor A1 (LF-A1), a factor previously shown to regulate the transcription of the .alpha.-1 antitrypsin, apolipoprotein A1 and pyruvate kinase genes.