The evasion from apoptosis is a common strategy adopted by most tumors, and inhibitors of apoptosis proteins (IAPs) are among the most studied molecular and therapeutic targets. BIRC3 (cellular IAP2) and BIRC5 (survivin) are two of the eight members of the human IAPs family. This family is characterized by the presence of the baculoviral IAP repeat (BIR) domains, involved in protein-protein interactions. In addition to the BIR domains, IAPs also contain other important domains like the C-terminal ubiquitin-conjugating (UBC) domain, the caspase recruitment (CARD) domain and the C-terminal Ring zinc-finger (RING) domain. BIRC3 and BIRC5 have been characterized in some solid and hematological tumors and are therapeutic targets for the family of drugs called “Smac mimetics”. Many evidences point to the pro-survival and antiapoptotic role of BIRC3 in cancer cells, however, not all the data are consistent and the resulting picture is heterogeneous. For instance, BIRC3 genetic inactivation due to deletions or point mutations is consistently associated to shorter progression free survival and poor prognosis in chronic lymphocytic leukemia patients. BIRC3 inactivation has also been associated to chemoimmunotherapy resistance. On the contrary, the progression from low grade gliomas to high grade gliomas is accompanied by BIRC3 expression increase, which bears relevant prognostic consequences. Due to the relationship between BIRC3, MAP3K14 and the non-canonical NF-kB pathway, BIRC3 inactivation bears consequences also on the tumor cells relying on NF-kB pathway to survive. BIRC5, on the contrary, is commonly considered an anti-apoptotic molecule, promoting cell division and tumor progression and it is widely regarded as potential therapeutic target. The present manuscript collects and reviews the most recent literature concerning the role played by BIRC3 and BIRC5 in cancer cells, providing useful information for the choice of the best therapeutic targets.

中文翻译：

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BIRC3和BIRC5：癌症中的多方面抑制剂

逃避细胞凋亡是大多数肿瘤采用的常见策略，细胞凋亡蛋白抑制剂 (IAPs) 是研究最多的分子和治疗靶点之一。BIRC3（细胞 IAP2）和 BIRC5（生存素）是人类 IAP 家族的八个成员中的两个。该家族的特点是存在参与蛋白质-蛋白质相互作用的杆状病毒 IAP 重复 (BIR) 结构域。除了 BIR 结构域，IAP 还包含其他重要结构域，如 C 末端泛素结合 (UBC) 结构域、半胱天冬酶募集 (CARD) 结构域和 C 末端环锌指 (RING) 结构域。BIRC3 和 BIRC5 已在一些实体瘤和血液肿瘤中得到表征，并且是称为“Smac 模拟物”的药物家族的治疗靶点。许多证据表明 BIRC3 在癌细胞中的促生存和抗凋亡作用，然而，并非所有数据都是一致的，并且结果是异质的。例如，由于缺失或点突变导致的 BIRC3 基因失活始终与慢性淋巴细胞白血病患者的无进展生存期较短和预后不良有关。BIRC3 失活也与化学免疫疗法抗性有关。相反，从低级别胶质瘤到高级别胶质瘤的进展伴随着 BIRC3 表达的增加，这具有相关的预后后果。由于 BIRC3、MAP3K14 和非经典 NF-kB 通路之间的关系，BIRC3 失活也对依赖 NF-kB 通路生存的肿瘤细胞产生影响。相反，BIRC5，通常认为是一种抗凋亡分子，可促进细胞分裂和肿瘤进展，并被广泛认为是潜在的治疗靶点。本手稿收集并回顾了有关 BIRC3 和 BIRC5 在癌细胞中所起作用的最新文献，为选择最佳治疗靶点提供有用信息。