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Inhibition of the biosynthesis of SRP polypeptides and secretory proteins by aflatoxin B-1 can disrupt protein targeting

  • 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 absenceCell 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.zeige mehrzeige weniger

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Metadaten
Verfasserangaben:Jasbir Singh, Harinder M. Dani, Reeta SharmaORCiDGND, Pablo SteinbergORCiDGND
DOI:https://doi.org/10.1027/cbf.1285
ISSN:0263-6484
Pubmed ID:https://pubmed.ncbi.nlm.nih.gov/16206272
Titel des übergeordneten Werks (Englisch):Cell biochemistry and function
Verlag:Wiley
Verlagsort:Chichester
Publikationstyp:Wissenschaftlicher Artikel
Sprache:Englisch
Datum der Erstveröffentlichung:03.10.2005
Erscheinungsjahr:2006
Datum der Freischaltung:04.05.2020
Freies Schlagwort / Tag:SRP; aflatoxin B-1; protein targeting; protein translocation; western blotting
Band:24
Seitenanzahl:4
Erste Seite:507
Letzte Seite:510
Organisationseinheiten:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie
DDC-Klassifikation:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Peer Review:Referiert
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