Synthetic peptides and non-peptidic molecules as probes of structure and function of Bcl-2 family proteins and modulators of apoptosis
Synthetic peptides and non-peptidic molecules as probes of structure and function of Bcl-2 family proteins and modulators of apoptosis
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DOI：
10.1023/a:1012481406064
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发表时间：
2001-12-01
期刊：
影响因子：
7.2
通讯作者：
Huang, Z
中科院分区：
文献类型：
--
作者：
Liu, D;Huang, Z
Bcl-2家族包括越来越多的在调节细胞凋亡或程序性细胞死亡中起重要作用的蛋白质。该家族的成员表现出多种生物学功能，可以抑制或促进细胞死亡信号。一些Bcl-2家族成员如抑制细胞凋亡的异常基因表达在多种人类癌症中被发现，并通过干扰化疗药物引发的细胞死亡信号，有助于肿瘤细胞对常规治疗的抵抗。因此，阐明Bcl-2家族的结构功能和机制对于理解细胞死亡和存活的一些基本原理，以及开发潜在的治疗方法来控制病理过程中的细胞凋亡具有重要的实用价值。从Bcl-2家族蛋白同源或异质结构域衍生的合成肽可能介导不同的生物活性，与全长肽相比，它们提供了简化和实验上更易于处理的模型来解剖和分析这些蛋白的复杂功能作用。通过随机筛选天然产物或通过合理的基于结构的技术设计的非肽分子可以通过靶向Bcl-2家族成员蛋白的类似活性位点来模拟合成肽的作用。本文综述了近年来利用这些合成肽和非肽类模拟分子来了解Bcl-2家族蛋白的结构和功能的研究进展，并讨论了它们在细胞内凋亡信号调节和研究中的应用。
The Bcl-2 family includes a growing number of proteins that play an essential role in regulating apoptosis or programmed cell death. Members of this family display diverse biological functions and can either inhibit or promote cell death signals. Abnormal gene expression of some Bcl-2 family members such as Bcl-2 that inhibits apoptosis is found in a wide variety of human cancers and contributes to the resistance of tumor cells to conventional therapies through interfering with the cell death signals triggered by chemotherapeutic agents. As such, elucidating the structure-function and mechanism of the Bcl-2 family is important for understanding some of the fundamental principles underling the death and survival of cells and of practical value for developing potential therapeutics to control apoptosis in pathological processes. Synthetic peptides derived from homologous or heterogeneous domains in Bcl-2 family proteins that might mediate different biological activities provide simplified and experimentally more tractable models as compared to their full-length counterparts to dissect and analyze the complex functional roles of these proteins. Non-peptidic molecules identified from random screening of natural products or designed by rational structure-based techniques can mimic the effect of synthetic peptides by targeting similar active sites on a Bcl-2 family member protein. In this article, we review recent progress in using these synthetic peptides and non-peptidic mimic molecules to obtain information about the structure and function of Bcl-2 family proteins and discuss their application in modulating and studying intracellular apoptotic signaling.