SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein
SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein
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DOI：
10.1016/s1097-2765(00)80336-6
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发表时间：
1999-09-01
期刊：
影响因子：
16
通讯作者：
Look, AT
中科院分区：
文献类型：
--
作者：
Inukai, T;Inoue, A;Look, AT
E2 A-HLF融合基因通过干扰凋亡信号传导的早期步骤转化人前B淋巴细胞。在E2 A-HLF反应基因的搜索，我们确定了锌指转录因子，SLUG，其产品属于蜗牛家族的发育调控蛋白。重要的是，SLUG与C. elegans，其在神经元特异性细胞死亡途径中作用于CES-2的下游。与CES-1作为抗凋亡转录因子的假定作用一致，SLUG在促进去除细胞因子的IL-3依赖性鼠pro-B细胞的存活方面几乎与Bcl-2或Bcl-x（L）一样活跃。我们的结论是，SLUG是一个进化上保守的转录抑制因子，其激活E2 A-HLF促进异常生存和最终的恶性转化的哺乳动物前B细胞，否则预定为凋亡死亡。
The E2A-HLF fusion gene transforms human pro-B lymphocytes by interfering with an early step in apoptotic signaling. In a search for E2A-HLF-responsive genes, we identified a zinc finger transcription factor, SLUG, whose product belongs to the Snail family of developmental regulatory proteins. Importantly, SLUG bears close homology to the CES-1 protein of C. elegans, which acts downstream of CES-2 in a neuron-specific cell death pathway. Consistent with the postulated role of CES-1 as an antiapoptotic transcription factor, SLUG was nearly as active as Bcl-2 or Bcl-x(L) in promoting the survival of IL-3-dependent murine pro-B cells deprived of the cytokine. We conclude that SLUG is an evolutionarily conserved transcriptional repressor whose activation by E2A-HLF promotes the aberrant survival and eventual malignant transformation of mammalian pro-B cells otherwise slated for apoptotic death.