Phosphorylation controls Ikaros's ability to negatively regulate the G1-S transition
Phosphorylation controls Ikaros's ability to negatively regulate the G1-S transition
复制标题
DOI：
10.1128/mcb.24.7.2797-2807.2004
复制
发表时间：
2004-04-01
影响因子：
5.3
通讯作者：
Georgopoulos, K
中科院分区：
文献类型：
--
作者：
Gómez-del Arco, P;Maki, K;Georgopoulos, K
Ikaros 是淋巴细胞增殖反应的关键调节因子。 Ikaros 的失活突变会导致抗原介导的淋巴细胞过度增殖以及白血病和淋巴瘤的快速发展。在这里，我们表明，Ikaros 负向调节 G(1)-S 转变的能力可以通过外显子 8 中富含丝氨酸/苏氨酸的保守区域 (p1) 的磷酸化来调节。p1 中的 Ikaros 磷酸化是在 G(1)-S 转变过程中诱导的。阻止 p1 磷酸化的突变会增加 Ikaros 阻碍细胞周期进程的能力及其对 DNA 的亲和力。酪蛋白激酶 II 的淋巴细胞活性增加会导致转化，是 Ikaros III 磷酸化的关键参与者。因此，我们提出，Ikaros 作为 G(1)-S 转变调节剂的活性是通过响应下调其 DNA 结合活性的信号事件的磷酸化来控制的。
Ikaros is a key regulator of lymphocyte proliferative responses. Inactivating mutations in Ikaros cause antigen-mediated lymphocyte hyperproliferation and the rapid development of leukemia and lymphoma. Here we show that Ikaros's ability to negatively regulate the G(1)-S transition can be modulated by phosphorylation of a serine/threonine-rich conserved region (p1) in exon 8. Ikaros phosphorylation in p1 is induced during the G(1)-S transition. Mutations that prevent phosphorylation in p1 increase Ikaros's ability to impede cell cycle progression and its affinity for DNA. Casein kinase II, whose increased activity in lymphocytes leads to transformation, is a key player in Ikaros Ill phosphorylation. We thus propose that Ikaros's activity as a regulator of the G(1)-S transition is controlled by phosphorylation in response to signaling events that down-modulate its DNA binding activity.