CaMca1 is the only metacaspase in Candida albicans, which shows structural homology to the mammalian caspases. CaMca1 consists of the caspase domain, the P20 and P10 regions, and the conserved catalytic histidine-cysteine dyad that is required for executing apoptosis in C. albicans. However, little is known about the proteolytic processing of CaMca1 or its activation under apoptosis-inducing conditions. To understand the regulation of this process, we characterized CaBir1 which is the single IAP (inhibitor-of-apoptosis protein) in C. albicans. IAPs are a family of proteins whose members all harbor a BIR (baculovirus IAP repeat) domain and negatively regulate apoptosis by inhibiting caspases. We found that the Cabir1/Cabir1 deletion mutant exhibited increased apoptotic phenotypes, such as ROS accumulation, nuclear segmentation, and cell survival, under apoptosis-inducing conditions. Examination of CaMca1 cleavage patterns in response to various apoptotic stresses revealed that these cleavages were stress-specific and dependent on the catalytic histidine-cysteine residues of CaMca1. The Cabir1/Cabir1 mutation was not associated with altered CaMca1 processing with or without apoptotic stimuli, but the Cabir1/Cabir1 mutant exhibited significantly increased caspase-like activities. These results suggest that CaBir1 acts as an apoptosis inhibitor by regulating caspase-like activity, but not CaMca1 processing.

CaMca1 是白色念珠菌中唯一的间半胱天冬酶，它显示出与哺乳动物半胱天冬酶的结构同源性。CaMca1 由 caspase 结构域、P20 和 P10 区域以及保守的催化组氨酸-半胱氨酸二分体组成，这是在白色念珠菌中执行细胞凋亡所需的。然而，关于 CaMca1 的蛋白水解过程或其在诱导细胞凋亡的条件下的激活知之甚少。为了了解这个过程的调控，我们对 CaBir1 进行了表征，它是白色念珠菌中的单一 IAP（凋亡抑制剂蛋白）。IAP 是一个蛋白质家族，其成员都包含一个 BIR（杆状病毒 IAP 重复）结构域，并通过抑制半胱天冬酶负向调节细胞凋亡。我们发现Cabir1/Cabir1在诱导凋亡的条件下，缺失突变体表现出增加的凋亡表型，例如 ROS 积累、核分割和细胞存活。对响应于各种凋亡应激的 CaMca1 裂解模式的检查表明，这些裂解是应激特异性的，并且依赖于 CaMca1 的催化组氨酸-半胱氨酸残基。所述Cabir1 / Cabir1突变不与具有或不具有细胞凋亡刺激改变CaMca1处理相关联，但Cabir1 / Cabir1突变体显示出增加显著胱天蛋白酶样活性。这些结果表明 CaBir1 通过调节半胱天冬酶样活性而不是 CaMca1 加工作为细胞凋亡抑制剂。