Inhibition of the biosynthesis of SRP polypeptides and secretory proteins by aflatoxin B1 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 absence from these locations could disturb cell to cell communication leading to tumorigenesis.
Singh
Jasbir
J
Department of Biochemistry, Kurukshetra University, Kurukshetra-136119, India. jaid22in@rediffmail.com
Dani
Harinder M
HM
Sharma
R
R
Steinberg
Pablo
P
D016604:Aflatoxin B1 / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002469:Cell Separation; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011388:Prolactin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011498:Protein Precursors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018271:Signal Recognition Particle / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013329:Structure-Activity Relationship
D010455:Peptides; D011498:Protein Precursors; D018271:Signal Recognition Particle; C017671:preprolactin; D011388:Prolactin; D016604:Aflatoxin B1