Bcl-2 family proteins and the regulation of programmed cell death in leukemia and lymphoma.
Bcl-2 family proteins and the regulation of programmed cell death in leukemia and lymphoma.
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DOI：
10.1007/978-1-4613-1261-1_3
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发表时间：
1996
影响因子：
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通讯作者：
John Calvin Reed;T. Miyashita;S. Krajewski;S. Takayama;C. Aimé-sempé;S. Kitada;T. Sato;H. G. Wang;M. Harigai;M. Hanada;M. Krajewska;K. Kochel;J. Millán;H. Kobayashi
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文献类型：
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作者：
John Calvin Reed;T. Miyashita;S. Krajewski;S. Takayama;C. Aimé-sempé;S. Kitada;T. Sato;H. G. Wang;M. Harigai;M. Hanada;M. Krajewska;K. Kochel;J. Millán;H. Kobayashi
Bcl2基因家族的成员在调节细胞对多种凋亡刺激的相对敏感性和抵抗力方面发挥着核心作用。这个多基因家族的第一个成员，bcl2，是由于它与非霍奇金淋巴瘤常见的t(14；18)染色体易位有关而被发现[1-4]。在B细胞淋巴瘤中通过易位或在包括急性和慢性白血病在内的其他几种类型的癌症中通过其他机制解除对bcl2基因的调控，通过延长细胞存活而不是通过加速细胞分裂速度来促进肿瘤细胞的扩张[5-8]。Bcl2蛋白还可以保护肿瘤细胞免受辐射和几乎所有细胞毒性抗癌药物[9-12]诱导的凋亡，从而潜在地导致癌症患者的治疗失败[13-16]。最近在人类和其他哺乳动物中发现了另外几个bcl2的同源基因，揭示了一个多基因家族的存在[17-20]。此外，在一些DNA病毒中也发现了bcl2的同源物，包括EB病毒(EBV)，它在某些类型的非霍奇金淋巴瘤和霍奇金病的发病机制中发挥着重要作用[21]。有趣的是，bcl2基因家族中的一些成员与bcl2类似，具有抑制细胞死亡的功能，而另一些成员则是凋亡的促进者，与bcl2蛋白的作用相反。这些Bcl2家族蛋白中的许多能够通过形成同型和异型二聚体相互作用[17，22]，揭示了蛋白质-蛋白质相互作用在调节Bcl2家族蛋白功能中的重要作用，并提出了从药物上操纵生理细胞死亡途径的方法(见表1)。
Members of the bcl-2 gene family playa central role in regulating the relative sensitivity and resistance of cells to a wide variety of apoptotic stimuli. The first member of this multigene family, bcl-2, was discovered by virtue of its involvement in the t (14; 18) chromosomal translocations commonly found in non-Hodgkin's lymphomas [1-4]. Deregulation of the bcl-2 gene either by translocations in B-cell lymphomas or through other mechanisms in several other types of cancer, including acute and chronic leukemias, contributes to neoplastic cell expansion by prolonging cell survival rather than by accelerating rates of cell division [5-8]. The Bcl-2 protein also can protect tumor cells from apoptosis induced by radiation and nearly all cytotoxic anticancer drugs [9-12], thus potentially contributing to treatment failures in patients with cancer [13-16]. Several additional homologues of bcl-2 have recently been discovered in humans and other mammals, revealing the presence of a multigene family [17-20]. Moreover, homologues of bcl-2 have been discovered in some DNA viruses, including Epstein-Barr virus (EBV), which plays a significant role in the pathogenesis of some types of non-Hodgkin's lymphomas and Hodgkin's disease [21]. Interestingly, some members of the bcl-2 gene family function as inhibitors of cell death, similar to bcl-2, whereas others are promoters of apoptosis that oppose the actions of the Bcl-2 protein. Many of these Bcl-2 family proteins have the capacity to interact with each other through formation of homo-and heterotypic dimers [17, 22], revealing an important role for protein-protein interactions in the orchastration of Bcl-2 family protein function and suggesting approaches to pharmacologically manipulating the physiological cell death pathway (see table 1).