THE GROWTH TRANSFORMATION OF HUMAN-B CELLS INVOLVES SUPERINDUCTION OF HSP(70) AND HSP(90)
THE GROWTH TRANSFORMATION OF HUMAN-B CELLS INVOLVES SUPERINDUCTION OF HSP(70) AND HSP(90)
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DOI：
10.1006/viro.1993.1178
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发表时间：
1993-04-01
期刊：
影响因子：
3.7
通讯作者：
DOSCH, HM
中科院分区：
文献类型：
--
作者：
CHEUNG, RK;DOSCH, HM
eb病毒（EBV）是一种潜伏的人类疱疹病毒，与一系列恶性和非恶性疾病有关。EBV与B淋巴细胞上的CD21病毒受体结合并生长转化这些细胞；在易感（如免疫缺陷）宿主中，这种细胞迅速扩展成致命的淋巴瘤。病毒结合和感染触发一系列细胞事件，这些事件是转化的先决条件，类似于非致癌细胞激活事件，但在几个定量或定性方面有所不同。独特的跨膜Ca2+电流，Na+/H+交换，以及酪氨酸磷酸化和p56lck基因诱导表明，即使在转化过程的早期也具有致癌特异性。在本报告中，我们描述了两个额外的细胞基因家族，应激蛋白sp70和hsp90，在mRNA和蛋白水平上协调诱导，与热应激诱导完全不同，这种诱导依赖于ebv诱导的跨膜Ca2+电流。阻断诱导可阻止转化。动力学和诱导先决条件使这种反应与报道的热或病毒应激蛋白诱导反应截然不同。与p56lck一样，hsp诱导纯粹是受体后结合事件，不依赖于任何病毒基因的表达。诱导动力学在约12-16小时达到峰值，随后下降到控制水平，极大地扩展了转化途径中cd21依赖分支中元素的时间顺序图，并表明诱导热休克的特定作用不同于在其他细胞系统中观察到的细胞周期相关功能。
Epstein-Barr virus (EBV) is a latent human herpes virus associated with a range of malignant and non-malignant disorders. EBV binds to CD21 virus receptors on B lymphocytes and growth transforms these cells; in susceptible (e.g., immunodeficient) hosts such cells rapidly expand into fatal lymphomas. Virus binding and infection trigger a cascade of cellular events which are transformation prerequisite and analogous to non-oncogenic cell activation events but which differ in several quantitative or qualitative respects. Uniquetrans-membrane Ca2+currents, Na+/H+exchange, as well as tyrosine phosphorylation and p56lck-gene induction suggest that even early on the transformation process has oncogenic specificity. In this report we describe that two additional cellular gene families, the stress proteinshsp70andhsp90, are coordinately induced at mRNA and protein levels and, quite different fromhspinduction by thermal stress, this induction is dependent on EBV-inducedtrans-membrane Ca2+currents. Blockade ofhspinduction prevents transformation. The kinetics and induction prerequisites set this response well apart from reported responses to thermal or viral stress protein induction. Like p56lck,hspinduction is purely a post-receptor binding event and not dependent on expression of any viral gene. The induction kinetics, with a peak at ∼ 12-16 hr and subsequent decline to control levels, considerably extend the chronological map of elements in the CD21-dependent branch of the transformation pathway and suggest a specific role of inducedhspdifferent from the cell cycle-related functions observed in other cell systems.