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PMID: 6767247 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Synthesis and insertion of cytochrome P-450 into endoplasmic reticulum membranes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 77 ·No. 2 ·1980-02-00 ·Pages 965-9

Bar-Nun S, Kreibich G, Adesnik M, Alterman L, Negishi M, Sabatini DD

Abstract

Treatment of rats with phenobarbital leads to a substantial increase in levels of translatable liver cytochrome P-450 mRNA. This mRNA is primarily associated with ribosomes bound to endoplasmic reticulum membranes which in an in vitro system synthesized approximately 10 times more cytochrome P-450 than did free polysomes from the same animals. Cytochrome P-450 synthesized by rough microsomes in vitro appears to be directly inserted into the membranes because it was not released by a treatment with low detergent concentrations that released albumin and other microsomal content proteins. The amino-terminal amino acid sequence of cytochrome P-450 synthesized in an mRNA-dependent system resembles in hydrophobicity the signal segment of presecretory proteins and therefore may serve to insert the polypeptide into the membrane during synthesis. In contrast to the situation with secretory proteins and several other membrane proteins, however, the putative insertion signal of cytochrome P-450 is not removed by a membrane-associated peptidase and remains in the mature polypeptide.

MeSH Terms
Animals Apoproteins/metabolism Cytochrome P-450 Enzyme System/biosynthesis,genetics,metabolism Endoplasmic Reticulum/metabolism Enzyme Induction/drug effects Intracellular Membranes/metabolism Phenobarbital/pharmacology Protein Biosynthesis Protein Precursors/metabolism RNA, Messenger/genetics Rats Ribosomes/metabolism
Chemicals
Apoproteins Protein Precursors RNA, Messenger Cytochrome P-450 Enzyme System Phenobarbital
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bar-Nun S
Kreibich G
Adesnik M
Alterman L
Negishi M
Sabatini D D
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46 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.77.2.965
Published
1980-02-00
Pages
965-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC348404
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.77.2.965 PMC Full Text View journal details
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