The expression of proprotein convertase PACE4 is highly regulated by Hash-2 in placenta: possible role of placenta-specific basic helix-loop-helix transcription factor, human achaete-scute homologue-2.

摘要: PACE4 is a member of the mammalian subtilisin-like proprotein convertase (SPC) family, which contribute to activation transforming growth factor (TGF) beta family proteins. We previously reported that highly expressed in syncytiotrophoblasts human placenta [Tsuji et al. (2003) BIOCHIM: Biophys. Acta 1645, 95-104]. In this study, regulatory mechanism for expression was analyzed using placental choriocarcinoma cell line, BeWo cells. Promoter analysis indicated an E-box cluster (E4-E9) 5'-flanking region gene acts as negative element. The binding achaete-scute homologue 2 (Hash-2) shown by gel mobility-shift assay. overexpression Hash-2 caused marked decrease expression. When cells were grown under low oxygen (2%) conditions, decreased, while increased. both cases, other SPCs, such furin, PC5/6, and PC7/8, not affected. Further, found be developmentally regulated rat placenta. By situ hybridization, Mash-2 (mammalian 2) mRNA spongiotrophoblast layer where expressed. contrast, mainly labyrinthine detected. These results suggest down-regulated Hash-2/Mash-2 many bioactive proteins might activity.