Premium
Inhibition of the biosynthesis of SRP polypeptides and secretory proteins by aflatoxin B 1 can disrupt protein targeting
Author(s) -
Singh Jasbir,
Dani Harinder M.,
Sharma R.,
Steinberg Pablo
Publication year - 2005
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1285
Subject(s) - signal recognition particle , endoplasmic reticulum , biosynthesis , secretory protein , signal peptide , polysome , cytosol , protein biosynthesis , biochemistry , secretory pathway , microbiology and biotechnology , biology , secretion , membrane protein , chemistry , golgi apparatus , membrane , ribosome , gene , rna , peptide sequence , enzyme
Cell culture and western blotting studies revealed that aflatoxin B 1 (AFB 1 ) inhibits the biosynthesis of two of the constituent polypeptides of signal recognition particle (SRP) (SRP54 and 72). SRP escorts polyribosomes carrying signal peptides from free form in the cytosol to the bound form on endoplasmic reticulum (ER) membrane during protein targeting. These effects of AFB 1 on SRP biosynthesis may inhibit the formation of functional SRP. Our experiments have further shown that AFB 1 also inhibits the biosynthesis/translocation of a secretory protein, preprolactin, which fails to appear in the lumen of ER consequent to the treatment with this hepatocarcinogen. The results of the experiments presented in this article therefore enable us to infer for the first time that aflatoxin B 1 may inhibit the functioning of SRP as an escort and deplete the ER of polyribosomes for secretory protein synthesis. As these secretory proteins are important components of the plasma membrane, gap junctions and intercellular matrix, their absence from these locations could disturb cell to cell communication leading to tumorigenesis. Copyright © 2005 John Wiley & Sons, Ltd.