Androgenic regulation of phosphorylation and stability of nucleolar protein nucleolin in rat ventral prostate

Abstract

Nucleolin is an abundant nucleolar phosphoprotein which has been implicated as a factor in various stages of ribosome synthesis, including transcription. Since androgens exert a profound effect on the rRNA synthesis in the target organ prostate, we have examined the nature of androgenic regulation of the amount and phosphorylation of nucleolin in this tissue. Phosphorylation of prostatic nucleolin is catalyzed in part by heparin-sensitive casein kinase 2 (CK-2) and by another (heparin-insensitive) protein kinase. Both the amount and phosphorylation of prostatic nucleolin are profoundly sensitive to androgens. Rapid reduction in the level and phosphorylation of nucleolin occurs following androgen deprivation, which corresponds to the ensuing cessation of prostatic growth leading to involution. Further, the loss of nucleolin phosphorylation and its degradation appear to be concordant. Administration of a single injection of 5 alpha-dihydrotestosterone to castrated animals causes an early increase in the amount and phosphorylation of nucleolin, starting in the prereplicative phase in the prostatic cell nucleus. These data suggest that early androgenic regulation of nucleolin expression and phosphorylation may play a role in nucleolar control mechanisms relevant to prostatic cell growth.

Role of Protein Phosphorylation in Post-translational Regulation of Protein B23 during Programmed Cell Death in the Prostate Gland

“…In a previous report, we documented that expression and phosphorylation of protein B23 started to decline at a modest rate in the first 24 h after androgen withdrawal (26) and that by 48 h post-castration, B23 was undetectable despite the presence of B23 mRNA up to 7 days of androgen withdrawal (26). These changes in expression coincided with the decline in ribosome synthesis and the morphological alterations associated with apoptosis, suggesting that protein B23 might be involved in these processes (26).…”

“…The animals were maintained under standard conditions and were orchiectomized via the scrotal route under Metofane anesthesia as described previously (26).…”

“…These changes in expression coincided with the decline in ribosome synthesis and the morphological alterations associated with apoptosis, suggesting that protein B23 might be involved in these processes (26). In the present work, we have explored the mechanisms by which the prostatic glandular epithelium controls the expression of protein B23 during apoptosis.…”

“…Protein B23 is phosphorylated by protein kinase CK2 in interphase (22) and by p34 cdc2 kinase during mitosis (23). The expression and phosphorylation of the protein are enhanced in different cell types in response to mitogens, growth factors, and hormones, including androgen in the prostate, suggesting that protein B23 constitutes a common signal required for cell proliferation (23)(24)(25)(26)(27)(28).In a previous report, we documented that expression and phosphorylation of protein B23 started to decline at a modest rate in the first 24 h after androgen withdrawal (26) and that by 48 h post-castration, B23 was undetectable despite the presence of B23 mRNA up to 7 days of androgen withdrawal (26). These changes in expression coincided with the decline in ribosome synthesis and the morphological alterations associated with apoptosis, suggesting that protein B23 might be involved in these processes (26).…”

“…Protein B23 is phosphorylated by protein kinase CK2 in interphase (22) and by p34 cdc2 kinase during mitosis (23). The expression and phosphorylation of the protein are enhanced in different cell types in response to mitogens, growth factors, and hormones, including androgen in the prostate, suggesting that protein B23 constitutes a common signal required for cell proliferation (23)(24)(25)(26)(27)(28).…”