Mode of action of the hemin-controlled inhibitor of protein synthesis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 75 ·No. 1 ·1978-01-00 ·Pages 243-7

de Haro C, Datta A, Ochoa S

Abstract

Despite the finding that the hemin-controlled translational inhibitor in reticulocyte lysates is a cyclic AMP-independent protein kinase that phosphorylates the small subunit of the initiation factor eIF-2, the mechanism of inhibition of translation remained unexplained. Whereas treatment of hemin-containing lysates with inhibitor in the presence of ATP inhibited translation, the same treatment of highly purified eIF-2 did not affect its ability to form a ternary complex with initiator Met-tRNA and GTP or a 40S initiation complex. We have isolated from ribosomal salt washes a protein (eIF-2 stimulating protein) that enhances the capacity of unphosphorylated eIF-2 to form ternary or 40S initiation complexes but has no effect on the phosphorylated factor. At low concentrations, eIF-2 is virtually inactive without this stimulating protein. Therefore, the translational inhibitor acts by converting eIF-2 to a form that is not stimulated by the stimulating protein.

MeSH Terms

Heme/analogs & derivatives Hemin/pharmacology Peptide Chain Initiation, Translational/drug effects Peptide Initiation Factors Proteins/antagonists & inhibitors,isolation & purification,pharmacology Reticulocytes/metabolism Ribosomes/metabolism Sulfhydryl Reagents/pharmacology

Chemicals

Peptide Initiation Factors Proteins Sulfhydryl Reagents Heme Hemin

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

de Haro C

Datta A

Ochoa S

References (19)

19 references, click to expand

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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.75.1.243

Published

1978-01-00

Pages

243-7

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC411222

Subset

External Links

PubMed source DOI: 10.1073/pnas.75.1.243 PMC Full Text View journal details

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Mode of action of the hemin-controlled inhibitor of protein synthesis.

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