Chinnadurai G, Vijayalingam S, Rashmi R
Institute for Molecular Virology, Saint Louis University Health Sciences Center, Doisy Research Center, 1100 South Grand Blvd, St Louis, MO 63104, USA.
Oncogene. 2008 Dec;27 Suppl 1(Suppl 1):S20-9. doi: 10.1038/onc.2009.40.
BIK is the founding member of the BH3-only family pro-apoptotic proteins. BIK is predominantly localized in the ER and induces apoptosis through the mitochondrial pathway by mobilizing calcium from the ER to the mitochondria and remodeling the mitochondrial cristae. BIK-mediated apoptosis is mediated by selective activation of BAX. BIK also induces non-apoptotic cell death in certain cell types by unknown mechanisms. BIK is non-essential for animal development, but appears to be functionally redundant for certain developmental functions with BIM. BIK is implicated in the selection of mature B cells in humans. BIK is a pro-apoptotic tumor suppressor in several human tissues and its expression in cancers is prevented by chromosomal deletions encompassing the Bik locus or by epigenetic silencing. BIK appears to be a critical effector in apoptosis induced by toxins, cytokines and virus infection. Several anti-cancer drugs transcriptionally activate Bik gene expression through transcriptional pathways dependent on factors such as E2F and p53 or by removal of epigenetic marks on the chromatin. BIK appears to be a prominent target for anti-cancer drugs that inhibit proteasomal functions. BIK has also been used as a therapeutic molecule in gene therapy-based approaches to treat difficult cancers.
BIK是仅含BH3结构域的促凋亡蛋白家族的创始成员。BIK主要定位于内质网，并通过将钙从内质网转运至线粒体以及重塑线粒体嵴，经线粒体途径诱导细胞凋亡。BIK介导的细胞凋亡由BAX的选择性激活介导。BIK还通过未知机制在某些细胞类型中诱导非凋亡性细胞死亡。BIK对动物发育并非必需，但在某些发育功能上似乎与BIM功能冗余。BIK与人类成熟B细胞的选择有关。在几种人类组织中，BIK是一种促凋亡的肿瘤抑制因子，其在癌症中的表达可通过包含Bik基因座的染色体缺失或表观遗传沉默来阻止。BIK似乎是毒素、细胞因子和病毒感染诱导的细胞凋亡中的关键效应因子。几种抗癌药物通过依赖于E2F和p53等因子的转录途径或通过去除染色质上的表观遗传标记来转录激活Bik基因表达。BIK似乎是抑制蛋白酶体功能的抗癌药物的主要靶点。在基于基因治疗的方法中，BIK也被用作治疗难治性癌症的治疗分子。
