THE ADENOVIRUS E1A PROTEINS INDUCE APOPTOSIS, WHICH IS INHIBITED BY THE E1B 19-KDA AND BCL-2 PROTEINS
THE ADENOVIRUS E1A PROTEINS INDUCE APOPTOSIS, WHICH IS INHIBITED BY THE E1B 19-KDA AND BCL-2 PROTEINS
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DOI：
10.1073/pnas.89.16.7742
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发表时间：
1992-08-15
影响因子：
11.1
通讯作者：
WHITE, E
中科院分区：
文献类型：
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作者：
RAO, L;DEBBAS, M;WHITE, E
腺病毒E1A和E1B癌基因之间的合作是转化初级静止啮齿动物细胞所必需的。虽然E1A单独表达将刺激细胞增殖足以启动转化灶形成，但增殖不能持续，灶退化。19 kDa或55 kDa E1B癌蛋白与E1A的共表达通过克服这种细胞毒性反应而允许高频率转化。然而，没有E1B 19-kDa蛋白表达，转化体仍然容易诱导细胞死亡。活力的快速丧失与核小体内区域的DNA的溶核裂解和染色质凝聚一致，这是程序性细胞死亡（细胞凋亡）的标志。此外，一个已知的抑制细胞凋亡，Bcl-2原癌基因的过度表达，可以挽救E1A诱导的病灶变性。因此，E1A依赖性的细胞增殖刺激伴随着凋亡，从而不足以单独诱导转化。高频转化需要E1B 19-kDa蛋白编码的第二种功能来阻断细胞凋亡。
Cooperation between the adenovirus E1A and E1B oncogenes is required for transformation of primary quiescent rodent cells. Although expression of E1A alone will stimulate cell proliferation sufficient to initiate transformed focus formation, proliferation fails to be sustained and foci degenerate. Coexpression of either the 19-kDa or 55-kDa E1B oncoproteins with E1A permits high-frequency transformation by overcoming this cytotoxic response. Without E1B 19-kDa protein expression, however, transformants remain susceptible to induction of cell death. Rapid loss of viability is coincident with nucleolytic cleavage of DNA in intranucleosomal regions and chromatin condensation, hallmarks of programed cell death (apoptosis). Furthermore, overexpression of a known suppressor of apoptosis, the Bcl-2 protooncogene, can rescue E1A-induced focus degeneration. Thus E1A-dependent stimulation of cell proliferation is accompanied by apoptosis and thereby insufficient to singly induce transformation. High-frequency transformation requires a second function encoded by the E1B 19-kDa protein to block apoptosis.