Growth arrest and DNA damage-45 alpha (GADD45α)
Growth arrest and DNA damage-45 alpha (GADD45α)
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DOI：
10.1016/j.biocel.2008.06.018
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发表时间：
2009-05-01
影响因子：
4
通讯作者：
Richardson, Des R.
中科院分区：
文献类型：
--
作者：
Siafakas, A. Rosemary;Richardson, Des R.
细胞周期和生长的调节对于细胞存活是不可或缺的。控制增殖和细胞周期的复杂机制有很多。生长停滞和DNA损伤（GADD）诱导的基因家族通常在各种环境应激和药物治疗中上调。GADD 45 α是第一个被确定为被p53上调的应激诱导基因，也是p53同源物p63和p73的靶基因。当GADD45a被删除或抑制时，细胞表现出不受控制的增殖。此外，GADD45 α表达降低也被认为是一种生存机制，因为没有这种控制的癌细胞可以逃避凋亡途径，导致肿瘤发生增加。药物治疗可直接或间接上调GADD 45 α并促进细胞凋亡。由于GADD 45 α是控制癌细胞增殖的许多代谢途径的重要组成部分，因此它本身是一个值得进一步研究的新兴药物靶点。(C)2008爱思唯尔有限公司版权所有。
Regulation of cell cycle and growth is integral for cell survival. The intricate mechanisms that control proliferation and cell cycle are numerous. The growth arrest and DNA damage (GADD)-inducible gene family is often up-regulated in response to various environmental stresses and drug therapies. GADD45 alpha was the first stress-inducible gene determined to be up-regulated by p53 and is also a target for the p53 homologues, p63 and p73. When GADD45a is deleted or repressed, cells show uncontrolled proliferation. Furthermore, decreased GADD45 alpha expression is also considered a survival mechanism, as cancer cells without this control can evade the apoptotic pathway leading to increased tumourigenesis. Drug therapies can act to directly or indirectly up-regulate GADD45 alpha and promote apoptosis. As GADD45 alpha is an essential component of many metabolic pathways that control proliferating cancer cells, it presents itself as an emerging drug target worthy of further investigation. (C) 2008 Elsevier Ltd. All rights reserved.