丝氨酸/苏氨酸蛋白激酶GSK-3（糖原合成酶激酶-3）是很多信号通道的构成部分，包括那些在糖原生产、细胞凋亡和干细胞维持中所涉及的信号通道。这些通道中的其中一些已被与人类疾病联系在一起，而GSK-3抑制剂则被看作是糖尿病和阿尔茨海默氏症的可能治疗药物。
现在，GSK-3被发现在支持急性白血病的病情发展中扮演一个以前人们未曾料到的角色——这个角色与人们根据其在抑制某些癌症中被异常激发的信号通道中扮演的已知角色所做出的预测是相反的。比较矛盾的是，GSK-3支持由MLL（混合型白血病）致癌基因引起的一种与众不同的遗传性白血病亚型。在一个MLL白血病的小鼠模型中，GSK-3的抑制影响癌症病情的发展，说明它的确是一个候选药物作用目标。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 455, 1205-1209 (30 October 2008) | doi:10.1038/nature07284
Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy
Zhong Wang1, Kevin S. Smith1, Mark Murphy1, Obdulio Piloto1, Tim C. P. Somervaille1 & Michael L. Cleary1
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA
Abstract
Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine kinase that participates in numerous signalling pathways involved in diverse physiological processes. Several of these pathways are implicated in disease pathogenesis, which has prompted efforts to develop GSK3-specific inhibitors for therapeutic applications. However, before now, there has been no strong rationale for targeting GSK3 in malignancies. Here we report pharmacological, physiological and genetic studies that demonstrate an oncogenic requirement for GSK3 in the maintenance of a specific subtype of poor prognosis human leukaemia, genetically defined by mutations of the MLL proto-oncogene. In contrast to its previously characterized roles in suppression of neoplasia-associated signalling pathways, GSK3 paradoxically supports MLL leukaemia cell proliferation and transformation by a mechanism that ultimately involves destabilization of the cyclin-dependent kinase inhibitor p27Kip1. Inhibition of GSK3 in a preclinical murine model of MLL leukaemia provides promising evidence of efficacy and earmarks GSK3 as a candidate cancer drug target.
