Cellular and Molecular Biochemistry Research Laboratory (151), Minneapolis Veterans Affairs Medical Center, and Department of Laboratory Medicine and Pathology and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55417, USA.
Biochemistry. 2010 May 11;49(18):3842-52. doi: 10.1021/bi9021928.
Protein B23/nucleophosmin/numatrin (B23) is a key nucleolar/nuclear matrix-associated protein required for cell growth-related functions, such as rRNA synthesis. Protein kinase CK2 (CK2) (formerly casein kinase 2, a protein Ser/Thr kinase signal that is involved in cell growth and cell death) mediates phosphorylation of B23, thereby influencing its functional activity. Here we have delineated the dynamics of B23 and its link to CK2 status in response to altered growth stimuli and induction of apoptosis in cultured prostate cells and in rat prostate cells in vivo. Our studies employing PC-3 and ALVA-41 prostate cancer cells demonstrated colocalization of CK2 and B23 in the nucleus. Further, CK2 and B23 underwent coordinate modulation in the nucleus related to their nucleocytoplasmic shuttling in response to induction of apoptotic activity in cells caused by downregulation of CK2 or by treatment with other apoptosis-inducing agents. These alterations in nuclear association of B23 occurred in the absence of a significant change in the level of cytoplasmic B23. Similar studies in the in vivo model of rat prostate epithelial cells subjected to androgen deprivation (that resulted in loss of nuclear CK2 and induction of apoptosis) demonstrated dynamic modulation of nuclear matrix-associated B23 without a significant change in its cytoplasmic level. These changes were reversed by androgen-mediated growth response in the prostate. Our results suggest that CK2-mediated phosphorylation of B23 is essential for its retention in the nucleus and that coordinated nuclear localization of B23 and CK2 is dynamically regulated in response to altered growth status in the cell.
B23/nucleophosmin/numatrin（B23）是一种关键的核仁/核基质相关蛋白，对于细胞生长相关的功能，如 rRNA 合成，是必需的。蛋白激酶 CK2（CK2）（原称酪蛋白激酶 2，一种参与细胞生长和细胞死亡的蛋白丝氨酸/苏氨酸激酶信号）介导 B23 的磷酸化，从而影响其功能活性。在这里，我们描述了 B23 的动力学及其与 CK2 状态的关系，以响应培养的前列腺细胞和体内大鼠前列腺细胞中改变的生长刺激和诱导凋亡。我们的研究使用 PC-3 和 ALVA-41 前列腺癌细胞表明 CK2 和 B23 在细胞核中存在共定位。此外，CK2 和 B23 在细胞核中进行协调调节，与它们的核质穿梭有关，以响应细胞中 CK2 下调或用其他诱导凋亡的剂处理引起的凋亡活性诱导。这些 B23 的核内关联的改变发生在细胞质 B23 的水平没有显著变化的情况下。在雄激素剥夺的大鼠前列腺上皮细胞体内模型的类似研究中（导致核 CK2 丢失和诱导凋亡），表明核基质相关 B23 的动态调节，而其细胞质水平没有显著变化。这些变化在前列腺中的雄激素介导的生长反应中得到逆转。我们的结果表明，CK2 介导的 B23 磷酸化对于其在核内的保留是必需的，并且 B23 和 CK2 的协调核定位是动态调节的，以响应细胞中改变的生长状态。
