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中文摘要：
糖原合成酶激酶3β（ glycogen synthase kinase 3β， GSK-3β）作为细胞内主要的丝氨酸/苏氨酸家族激酶，其活性异常与多种疾病的发生发展密切相关。值得关注的是， GSK-3β对肿瘤进程的调节是双向的，当扮演“促瘤因子”角色的GSK-3β被抑制时，不可避免阻断了其“抑瘤因子”的功能，使得 Wnt/β-catenin 信号通路的激活，成为目前靶向肿瘤GSK-3β引起治疗矛盾的焦点。事实上，生物学的绝缘机制可以使GSK-3β在广泛参与细胞内众多信号通路的调节中互不干扰，从而决定了细胞命运。因此，深入了解 GSK-3β在不同信号系统中活性调节的具体机制，或者设计底物特异的竞争性抑制剂，对于在靶向GSK-3β的肿瘤治疗中采取选择性的权衡策略具有重大意义。
英文摘要：
As the major member of serine/threonine protein ki-nases family, glycogen synthase kinase 3β （ GSK-3β） has well characterized roles in the development of a variety of diseases. However, it is noticed that modulation of GSK-3β in tumor pro-gress is two-faced. Once the activity of GSK-3βas a“pro-onco-genic factor” is inhibited, opposing role as a“tumor suppressor”can also be disrupted, which will trigger the consequent side effect on activation of Wnt/β-catenin signaling pathway. The is-sue has placed a major obstacle to anti-GSK-3β in cancer treat-ment. In fact, functional compartmentalization of a large number of intracellular signaling events cross-talked with GSK-3β can prevent their mutual interference and determine the cell fate. Therefore, understanding the specific mechanisms of GSK-3β in regulation of diverse signaling systems or refinement of a sub-strate competitive inhibitor may have great significance to exploit approaches selectively target GSK-3β in tumor treatment.
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