Role of protein phosphorylation in post-translational regulation of protein B23 during programmed cell death in the prostate gland.
Protein B23 is a nucleolar and nuclear matrix-associated phosphoprotein that is involved in ribosome synthesis. Its expression and phosphorylation in rat ventral prostate, an androgen target organ, are profoundly influenced by androgens. Induction of programmed cell death (apoptosis) in the prostatic epithelium by androgen deprivation in the animal induces an early decline in protein B23 in the absence of a corresponding loss of protein B23 mRNA. We have now demonstrated that prostatic nuclei retain the ability to transcribe the B23 mRNA and that a significant amount of this mRNA persists even after 7 days of androgen deprivation when > 80% of the prostatic epithelial cells have undergone apoptosis. The B23 mRNA from these nuclei is also translatable in vitro. However, the majority of the B23 mRNA is associated with free and short-stretch polysomes, which may account for the castration-induced decline in synthesis of protein B23 in vivo. In addition, the mechanism of down-regulation of protein B23 in apoptotic prostatic cells appears to relate to two coordinate signals, which include loss of phosphorylation of the protein as well as the expression of a protease active toward dephosphorylated protein B23, under these conditions.
Tawfic
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Cellular and Molecular Biochemistry Research Laboratory (151), Department of Veterans Affairs Medical Center, Minneapolis, Minnesota 55417, USA.
Olson
M O
MO
Ahmed
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D000728:Androgens / Q000172:deficiency; D000818:Animals; D017209:Apoptosis; D006868:Hydrolysis; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic
D000728:Androgens; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D000090243:Nucleophosmin