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PMID: 7568236 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Recruitment of hepatocyte nuclear factor 4 into specific intranuclear compartments depends on tyrosine phosphorylation that affects its DNA-binding and transactivation potential.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 21 ·1995-10-10 ·Pages 9876-80

Ktistaki E, Ktistakis NT, Papadogeorgaki E, Talianidis I

Abstract

Hepatocyte nuclear factor 4 (HNF-4) is a prominent member of the family of liver-enriched transcription factors, playing a role in the expression of a large number of liver-specific genes. We report here that HNF-4 is a phosphoprotein and that phosphorylation at tyrosine residue(s) is important for its DNA-binding activity and, consequently, for its transactivation potential both in cell-free systems and in cultured cells. Tyrosine phosphorylation did not affect the transport of HNF-4 from the cytoplasm to the nucleus but had a dramatic effect on its subnuclear localization. HNF-4 was concentrated in distinct nuclear compartments, as evidenced by in situ immunofluorescence and electron microscopy. This compartmentalization disappeared when tyrosine phosphorylation was inhibited by genistein. The correlation between the intranuclear distribution of HNF-4 and its ability to activate endogenous target genes demonstrates a phosphorylation signal-dependent pathway in the regulation of transcription factor activity.

MeSH Terms

Animals Biological Transport Cell Compartmentation/drug effects Cell Nucleus/metabolism,ultrastructure Cells, Cultured Cytoplasm/metabolism DNA/metabolism DNA-Binding Proteins/metabolism Enzyme Inhibitors/pharmacology Fluorescent Antibody Technique, Indirect Genistein Hepatocyte Nuclear Factor 4 Isoflavones/pharmacology Phosphoproteins/genetics,metabolism Phosphorylation/drug effects Protein Binding Protein-Tyrosine Kinases/antagonists & inhibitors Recombinant Proteins/metabolism Trans-Activators/metabolism Transcription Factors/genetics,metabolism Transcriptional Activation Transfection

Chemicals

DNA-Binding Proteins Enzyme Inhibitors Hepatocyte Nuclear Factor 4 Isoflavones Phosphoproteins Recombinant Proteins Trans-Activators Transcription Factors DNA Genistein Protein-Tyrosine Kinases

Authors & Affiliations

4 authors, click to expand affiliations / ORCID

Ktistaki E

Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Herakleion Crete, Greece.

Ktistakis N T

Papadogeorgaki E

Talianidis I

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.92.21.9876

Published

1995-10-10

Pages

9876-80

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC40905

Subset

External Links

PubMed source DOI: 10.1073/pnas.92.21.9876 PMC Full Text View journal details

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Recruitment of hepatocyte nuclear factor 4 into specific intranuclear compartments depends on tyrosine phosphorylation that affects its DNA-binding and transactivation potential.

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