Rapid activation by interferon alpha of a latent DNA-binding protein present in the cytoplasm of untreated cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 4 ·1989-02-00 ·Pages 1203-7

Dale TC, Imam AM, Kerr IM, Stark GR

Abstract

The highly conserved interferon (IFN)-stimulated regulatory elements of the human genes 6-16 and 9-27 bind to one or more proteins (E factor) detected in extracts of human Bristol 8 B cells or human foreskin fibroblast cells treated with IFN-alpha. E factor is not detectable in extracts of untreated cells and appears in IFN-treated cells within less than 1 min in a form extractable with low salt and thus presumably not bound to DNA. After a few more minutes, the level of this form decreases in parallel with the increase of a form extractable only with high salt and thus presumably bound to DNA. Induction of E factor by IFN-alpha can occur in nuclei-free cytoplasts, whereas no E factor was detected in IFN-treated nucleoplasts. Together, these results suggest a model for signal transduction in which latent E factor, located in the cytoplasm, is activated or released from an inhibitor very rapidly upon binding of IFN-alpha to its receptor. Active E factor can then migrate to the nucleus, where it binds to the IFN-stimulated regulatory elements of IFN-regulated genes, activating their transcription.

MeSH Terms

Cell Line Cells, Cultured Cytoplasm/metabolism DNA-Binding Proteins/metabolism Flow Cytometry Genes, Regulator/drug effects Humans Interferon Type I/pharmacology Oligonucleotide Probes Recombinant Proteins Signal Transduction

Chemicals

DNA-Binding Proteins Interferon Type I Oligonucleotide Probes Recombinant Proteins

Authors & Affiliations

4 authors, click to expand affiliations / ORCID

Dale T C

Imperial Cancer Research Fund Laboratories, London, United Kingdom.

Imam A M

Kerr I M

Stark G R

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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.86.4.1203

Published

1989-02-00

Pages

1203-7

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC286654

Subset

External Links

PubMed source DOI: 10.1073/pnas.86.4.1203 PMC Full Text View journal details

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Rapid activation by interferon alpha of a latent DNA-binding protein present in the cytoplasm of untreated cells.

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