Retinoid targets for apoptosis induction
Retinoid targets for apoptosis induction
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DOI：
10.1038/sj.onc.1207109
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发表时间：
2003-12-08
期刊：
影响因子：
8
通讯作者：
Piedrafita, FJ
中科院分区：
文献类型：
--
作者：
Pfahl, M;Piedrafita, FJ
某些合成的类维生素A相关分子通过一种新的不依赖于核类维生素A受体的类维生素A作用机制诱导癌细胞凋亡。这些化合物靶向蛋白激酶和蛋白磷酸酶以触发导致细胞凋亡的信号转导途径。类维生素A激动剂如CD 437通过抑制磷酸酶MKP-1激活应激激酶，而类维生素A拮抗剂MX 781抑制存活激酶IKK。这些类维生素A介导的信号传导途径在线粒体处会聚，在线粒体处它们引起细胞色素c的释放和随后的Apaf-1依赖的半胱天冬酶活化。类维生素A靶点介导其凋亡活性的鉴定将增强我们对这种新的类维生素A作用机制的理解，以允许适当优化目前可用的化合物作为新型抗癌剂进入临床。
Certain synthetic retinoid-related molecules induce apoptosis in cancer cells through a novel mechanism of retinoid action that is independent of the nuclear retinoid receptors. These compounds target protein kinases and protein phosphatases to trigger signal transduction pathways that lead to apoptosis. Whereas retinoid agonists such as CD437 activate stress kinases via inhibition of the phosphatase MKP-1, the retinoid antagonist MX781 inhibits the survival kinase IKK. These retinoid-mediated signaling pathways converge at the mitochondria, where they cause the release of cytochrome c and subsequent Apaf-1-dependent activation of caspases. Identification of the retinoid targets that mediate their apoptotic activity will enhance our understanding of the mechanism of this novel retinoid action, to allow appropriate optimization of currently available compounds to advance into the clinic as novel anticancer agents.