探討半胱胺酸蛋白酶-14藉由降低GCM1的活性 而抑制胎盤滋養層細胞的分化

Abstract

Human GCM1 is a placenta-specific transcription factor, which plays an important role in regulation of trophoblast fusion for the formation of chorionic villus. We recently identified caspase-14 as a GCM1-associated protein using a tandem affinity purification approach coupled with mass spectrometry. Previous studies have shown that caspase-14 is associated with terminal differentiation of keratinocytes in the epidermis. Interestingly, recent studies have also shown that caspase-14 is expressed in the human placental trophoblast cells and may inhibit their differentiation. How caspase-14 regulates trophoblast cell differentiation is not known. In this study, we demonstrated that caspase-14 interacts with GCM1 in vitro and in vivo. Immunohistochemical analysis revealed that caspase-14 is located in cytotrophoblast cells and GCM1 in the syncytiotrophoblast layer in first-trimester placentas. In contrast, both caspase-14 and GCM1 proteins were detected in the syncytiotrophoblast layer in term placentas. We further demonstrated that caspase-14 suppresses the transcriptional activity of GCM1 and that the expression of GCM1 target genes is elevated when caspase-14 is knocked down by RNA interference. Importantly, we showed that caspase-14 blocks the interaction between CBP and GCM1 to prevent GCM1 acetylation by CBP and thereby decrease the protein stability of GCM1. Our study suggests that caspase-14 may repress GCM1 activity to inhibit trophoblast differentiation.