Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis.

摘要: Abstract Cellular cholesterol homeostasis is controlled by sterol-regulated proteolysis of membrane-bound transcription factors called sterol-regulatory element binding proteins (SREBPs). CPP32, a cysteine protease, was shown previously to cleave SREBP-1 and SREBP-2 in vitro at an aspartic acid between the basic helix-loop-helix leucine zipper domain first trans-membrane domain, liberating transcriptionally active fragment. Here, we show that CPP32 exists inactive 32 kDa form Chinese hamster ovary (CHO) cells. When apoptosis induced with protein kinase inhibitor staurosporine, cleaved subunits 20 10 protease. Under these conditions were both cleaved, N-terminal fragments found nuclear extracts. Similar results obtained human U937 cells undergo anti-Fas etoposide. The apoptosis-induced cleavage SREBPs not suppressed sterols, indicating are mediated different proteases. CHO expressing mutant Asp--> Ala mutation site showed but no cleavage. These data consistent emerging concept central mediator apoptosis. They also indicate SREBPs, like poly (ADP) ribose polymerase, during programmed cell death.