Apoptosis inhibition in cancer cells: A novel molecular pathway that involves BAG3 protein
Apoptosis inhibition in cancer cells: A novel molecular pathway that involves BAG3 protein
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DOI：
10.1016/j.biocel.2007.03.007
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发表时间：
2007-01-01
影响因子：
4
通讯作者：
Turco, Maria Caterina
中科院分区：
文献类型：
--
作者：
Rosati, Alessandra;Ammirante, Massimo;Turco, Maria Caterina
应激诱导的细胞凋亡调节肿瘤的发病机制和对治疗的反应。事实上，细胞转化诱导应激反应，在肿瘤细胞中，通过改变细胞凋亡调节剂来克服应激反应;另一方面，抗肿瘤疗法在很大程度上触发细胞凋亡应激途径，其损伤导致抗性。因此，研究肿瘤发生发展和治疗反应中肿瘤调节分子的作用对于我们理解这些过程具有重要意义。在调节细胞凋亡的分子中，BAG共伴侣蛋白家族的成员BAG 3正在发挥作用。共享BAG结构域的蛋白质的特征在于它们与多种配偶体（热休克蛋白、类固醇激素受体、Raf-1等）相互作用，参与调节许多细胞过程，包括增殖和凋亡。BAG 3，也称为CAIR-1或Bis，与热休克蛋白（Hsp）70形成复合物。这有助于多肽折叠，可以介导蛋白质递送到蛋白酶体，并且能够通过干扰细胞色素c释放、细胞色素体组装和死亡过程中的其他事件来调节细胞凋亡。它最近已被证明，在人类原发性淋巴细胞和成髓细胞白血病和其他肿瘤细胞类型，BAG 3的表达维持细胞的生存和耐药性的基础上，通过downtromodulation的apoptosis.This审查总结的结果，分配一个凋亡的作用，BAG 3在某些肿瘤细胞类型和确定的蛋白作为一个候选目标的治疗。(c)2007爱思唯尔有限公司保留所有权利。
Stress-induced apoptosis regulates neoplasia pathogenesis and response to therapy. Indeed, cell transformation induces a stress response, that is overcome, in neoplastic cells, by alterations in apoptosis modulators; on the other hand, antineoplastic therapies largely trigger the apoptosis stress pathway, whose impairment results in resistance. Therefore, the study of the roles of apoptosismodulating molecules in neoplasia development and response to therapy is of key relevance for our understanding of these processes. Among molecules that regulate apoptosis, a role is emerging for BAG3, a member of the BAG co-chaperone protein family. Proteins that share the BAG domain are characterized by their interaction with a variety of partners (heat shock proteins, steroid hormone receptors, Raf-1 and others), involved in regulating a number of cellular processes, including proliferation and apoptosis. BAG3, also known as CAIR-1 or Bis, forms a complex with the heat shock protein (Hsp) 70. This assists polypeptide folding, can mediate protein delivery to proteasome and is able to modulate apoptosis by interfering with cytochrome c release, apoptosome assembly and other events in the death process. It has been recently shown that, in human primary lymphoid and myeloblastic leukemias and other neoplastic cell types, BAG3 expression sustains cell survival and underlies resistance to therapy, through downtrodulation of apoptosis.This review summarizes findings that assign an apoptotic role to BAG3 in some neoplastic cell types and identify the protein as a candidate target of therapy. (c) 2007 Elsevier Ltd. All rights reserved.