Saleeart Anchulee, Mongkorntanyatip Karntichar, Sangsuriya Pakkakul, Senapin Saengchan, Rattanarojpong Triwit, Khunrae Pongsak
Department of Microbiology, Faculty of Science, King Mongkut's University of Technology Thonburi, Bangkok 10140, Thailand.
Aquatic Molecular Genetics and Biotechnology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 113 Paholyothin Road, Klong 1, Klongluang, Pathumthani 12120, Thailand.
Fish Shellfish Immunol. 2016 Aug;55:393-400. doi: 10.1016/j.fsi.2016.06.013. Epub 2016 Jun 18.
Apoptosis is an essential mechanism in multicellular organisms which results in the induction of cell death. Important apoptotic proteins, including high temperature requirement A2 (PmHtrA2; also known as serine protease), inhibitor of apoptosis protein (PmIAP) and Pm caspase, have been previously identified in black tiger shrimp, Penaeus monodon. However, the relevance among these proteins in apoptosis regulation has not been established yet in shrimp. Here, we showed that PmHtrA2 was able to interact with PmIAP and the binding of the two proteins was mediated by the BIR2 domain of PmIAP. In addition, the BIR2 of PmIAP was shown to be able to inhibit Pm caspase activity. The inhibitory effect of the BIR2 domain on Pm caspase was impaired under the presence of the IBM peptide of PmHtrA2, implying a role for PmHtrA2 in apoptosis activation. Our combined results suggested that P. monodon possesses a conserved mechanism by which the caspase-3 activity is modulated by HtrA2 and IAP, as previously seen in insects and mammals.
细胞凋亡是多细胞生物中导致细胞死亡的一种重要机制。重要的凋亡蛋白，包括高温需求蛋白A2（PmHtrA2；也称为丝氨酸蛋白酶）、凋亡抑制蛋白（PmIAP）和Pm半胱天冬酶，此前已在黑虎虾（斑节对虾）中被鉴定出来。然而，在虾中这些蛋白在凋亡调控中的相关性尚未确定。在此，我们表明PmHtrA2能够与PmIAP相互作用，且这两种蛋白的结合由PmIAP的BIR2结构域介导。此外，PmIAP的BIR2被证明能够抑制Pm半胱天冬酶的活性。在PmHtrA2的IBM肽存在的情况下，BIR2结构域对Pm半胱天冬酶的抑制作用受损，这意味着PmHtrA2在凋亡激活中发挥作用。我们的综合结果表明，斑节对虾拥有一种保守机制，即半胱天冬酶-3的活性受HtrA2和IAP调控，这与之前在昆虫和哺乳动物中观察到的情况相同。
