Liver enriched transcription factor

US7368293B2 · kind B2 · 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: Aug 9, 2002
• Grant date: May 6, 2008
• Expiry date: May 1, 2023

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K38/00
• 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 α-1 antitrypsin, apolipoprotein A1 and pyruvate kinase genes.