Effects of an inhibitor of tripeptidyl peptidase II (Ala-Ala-Phe-chloromethylketone) and its combination with an inhibitor of the chymotrypsin-like activity of the proteasome (PSI) on apoptosis, cell cycle and proteasome activity in U937 cells.
AAF-AMC is not a specific TPP II substrate, since it is also hydrolyzed by purified proteasomes. Moreover, AAF-cmk, claimed to be a specific TPP II inhibitor, also inhibits the chymotrypsin-like activity of the proteasome. While AAF-cmk itself is mildly cytostatic to U-937 cells and induces cell cycle block in G1, its combination with PSI does not induce an increase in the cytostatic/cytotoxic effects. This suggests that TPP II is possibly less important for cell metabolism than it was previously believed and it is less probable that it can be able to fully compensate for the loss of the proteasome function.
Bury
M
M
Department of Histology and Embryology, Medical Academy, Warsaw, Poland.
Młynarczuk
I
I
Pleban
E
E
Hoser
G
G
Kawiak
J
J
Wójcik
C
C
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000626:Aminopeptidases; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D005434:Flow Cytometry; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex; D012697:Serine Endopeptidases / Q000378:metabolism*; D014361:Trypsin Inhibitors / Q000494:pharmacology*; D020298:U937 Cells
D000590:Amino Acid Chloromethyl Ketones; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; C055604:alanyl-alanyl-phenylalanine chloromethyl ketone; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex