Li Gang, Liao Man, Li Shuang, You Jia, Wang Jun, Lei Wei, Yang Chunlei, Xu Haolun, Xiao He, Chen Haitao
Department of Urology, Wuhan Children's Hospital, Wuhan, Hubei 430016, P.R. China.
Exp Ther Med. 2021 Dec;22(6):1399. doi: 10.3892/etm.2021.10835. Epub 2021 Oct 1.
Inhibitors of apoptosis (IAPs) are a family of cell death inhibitors found in viruses and metazoans that physically interact with a variety of pro-apoptotic proteins and inhibit apoptosis induced by diverse stimuli. Melanoma IAP (ML-IAP) is a potent anti-apoptotic protein that is strongly upregulated in melanoma and confers protection against a variety of pro-apoptotic stimuli. In the present study, it was revealed that ML-IAP was expressed at high levels in testicular teratoma. Deletion and mutational analysis demonstrated that ML-IAP silencing significantly decreased P19 cell proliferation while inducing cell cycle arrest and apoptosis. ML-IAP knockdown significantly induced caspase-3/8/9-mediated apoptosis in P19 cells. In addition, metabolism and stemness maintenance in P19 cells were suppressed by ML-IAP knockdown. These results indicated that ML-IAP silencing is a powerful inducer of apoptosis mediated by cell death receptors and may function as a direct activator of downstream effector caspases.
凋亡抑制蛋白（IAPs）是一类在病毒和后生动物中发现的细胞死亡抑制因子，它们与多种促凋亡蛋白发生物理相互作用，并抑制由多种刺激诱导的细胞凋亡。黑色素瘤IAP（ML-IAP）是一种强效抗凋亡蛋白，在黑色素瘤中强烈上调，并赋予细胞对多种促凋亡刺激的保护作用。在本研究中，发现ML-IAP在睾丸畸胎瘤中高表达。缺失和突变分析表明，ML-IAP沉默显著降低P19细胞增殖，同时诱导细胞周期停滞和凋亡。ML-IAP敲低显著诱导P19细胞中caspase-3/8/9介导的凋亡。此外，ML-IAP敲低抑制了P19细胞的代谢和干性维持。这些结果表明，ML-IAP沉默是细胞死亡受体介导的凋亡的强力诱导剂，可能作为下游效应半胱天冬酶的直接激活剂发挥作用。
