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雄激素对大鼠腹侧前列腺中核仁蛋白核仁素磷酸化和稳定性的调节作用

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

作者信息

Tawfic S, Goueli S A, Olson M O, Ahmed K

机构信息

Department of Veterans Affairs Medical Center, Minneapolis, MN.

出版信息

Prostate. 1994;24(2):101-6. doi: 10.1002/pros.2990240208.

DOI:10.1002/pros.2990240208
PMID:8309845
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.

摘要

核仁素是一种丰富的核仁磷蛋白,已被认为是核糖体合成各个阶段(包括转录)中的一个因子。由于雄激素对靶器官前列腺中的rRNA合成有深远影响,我们研究了该组织中雄激素对核仁素数量和磷酸化的调节性质。前列腺核仁素的磷酸化部分由肝素敏感的酪蛋白激酶2(CK-2)和另一种(肝素不敏感)蛋白激酶催化。前列腺核仁素的数量和磷酸化对雄激素都极为敏感。雄激素剥夺后,核仁素的水平和磷酸化迅速降低,这与随后前列腺生长停止导致退化相对应。此外,核仁素磷酸化的丧失及其降解似乎是一致的。给去势动物单次注射5α-二氢睾酮会导致核仁素的数量和磷酸化早期增加,起始于前列腺细胞核的复制前期。这些数据表明,雄激素对核仁素表达和磷酸化的早期调节可能在与前列腺细胞生长相关的核仁控制机制中起作用。

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Androgenic regulation of phosphorylation and stability of nucleolar protein nucleolin in rat ventral prostate.雄激素对大鼠腹侧前列腺中核仁蛋白核仁素磷酸化和稳定性的调节作用
Prostate. 1994;24(2):101-6. doi: 10.1002/pros.2990240208.
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Induced expression of nucleolin phosphorylation-deficient mutant confers dominant-negative effect on cell proliferation.核仁素磷酸化缺陷型突变体的诱导表达对细胞增殖具有显性负效应。
PLoS One. 2014 Oct 14;9(10):e109858. doi: 10.1371/journal.pone.0109858. eCollection 2014.
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Systemic administration of antisense oligonucleotides simultaneously targeting CK2α and α' subunits reduces orthotopic xenograft prostate tumors in mice.
系统给予同时靶向 CK2α 和 α'亚基的反义寡核苷酸可减少小鼠原位异种移植前列腺肿瘤。
Mol Cell Biochem. 2011 Oct;356(1-2):21-35. doi: 10.1007/s11010-011-0943-x. Epub 2011 Jul 15.
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CK2beta is expressed in endometrial carcinoma and has a role in apoptosis resistance and cell proliferation.细胞周期蛋白依赖性激酶2β(CK2β)在子宫内膜癌中表达,并在抗凋亡和细胞增殖中发挥作用。
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Inactivation of nucleolin leads to nucleolar disruption, cell cycle arrest and defects in centrosome duplication.核仁素的失活会导致核仁破坏、细胞周期停滞以及中心体复制缺陷。
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