Stress sensor Gadd45 genes as therapeutic targets in cancer.
Stress sensor Gadd45 genes as therapeutic targets in cancer.
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发表时间：
2009
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通讯作者：
Alexandra Cretu;Xiaojin Sha;Jennifer S. Tront;B. Hoffman;D. Liebermann
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作者：
Alexandra Cretu;Xiaojin Sha;Jennifer S. Tront;B. Hoffman;D. Liebermann
Gadd 45基因参与对各种生理或环境应激源的应激信号应答，导致细胞周期停滞、DNA修复、细胞存活和衰老或凋亡。迄今为止积累的证据表明，Gadd 45蛋白作为应激传感器发挥作用，通过与其他细胞蛋白的复杂的物理相互作用来介导其活性，这些蛋白参与细胞周期调节和细胞对应激的反应。这些包括PCNA，p21，cdc 2/cyclinB 1，p38和JNK应激反应激酶。在多种类型的实体瘤以及造血系统恶性肿瘤中已经观察到Gadd 45的表达失调。此外，已经积累的证据表明，Gadd 45蛋白质与肿瘤细胞对各种癌症治疗剂的反应内在相关。因此，Gadd 45蛋白可能代表了一类新的癌症治疗干预靶点。需要更多的研究来更好地了解哪些Gadd 45应激反应功能可能是癌症治疗中化疗药物设计的目标。
Gadd45 genes have been implicated in stress signaling responses to various physiological or environmental stressors, resulting in cell cycle arrest, DNA repair, cell survival and senescence, or apoptosis. Evidence accumulated up to date suggests that Gadd45 proteins function as stress sensors, mediating their activity through a complex interplay of physical interactions with other cellular proteins that are implicated in cell cycle regulation and the response of cells to stress. These include PCNA, p21, cdc2/cyclinB1, and the p38 and JNK stress response kinases. Disregulated expression of Gadd45 has been observed in multiple types of solid tumors as well as in hematopoietic malignancies. Also, evidence has accumulated that Gadd45 proteins are intrinsically associated with the response of tumor cells to a variety of cancer therapeutic agents. Thus, Gadd45 proteins may represent a novel class of targets for therapeutic intervention in cancer. Additional research is needed to better understand which of the Gadd45 stress response functions may be targeted for chemotherapeutic drug design in cancer therapy.