Identification of a cysteine protease closely related to interleukin-1 beta-converting enzyme.
The present study describes the identification and molecular cloning of a new member of the interleukin-1 beta-converting enzyme (ICE) family denoted transcript Y (TY). TY is very closely related to both ICE (51% amino acid identity) and a protein named transcript X (TX) (75% amino acid identity) that we recently identified [Faucheu, C., Diu, A., Chan, A.W.E., Blanchet, A.-M., Miossec, C., Hervé, F.,Collard-Dutilleul, V., Gu, Y., Aldape, R., Lippke, J., Rocher, C., Su, M.S.-S., Livingston, D.J., Hercend, T. & Lalanne, J.-L. (1995) EMBO J. 14, 1914-1922]. The amino acids that are implicated in both the ICE catalytic site and in the PI aspartate-binding pocket are conserved in TY. Within the ICE gene family, TY belongs to a subfamily of proteins closely related to the prototype ICE protein. Using transfection experiments into mammalian cells, we demonstrate that TY has protease activity on its own precursor and that this activity is dependent on the presence of a cysteine residue at position 245. However, despite the close similarity between TY and ICE active sites, TY fails to process the interleukin-1 beta precursor. In addition, as already observed for ICE and TX, TY is able to induce apoptosis when overexpressed in COS cells. TY therefore represents a new member of the growing family of apoptosis-inducing ICE-related cysteine proteases.
Faucheu
C
C
Roussel-Uclaf, Romainville, France.
Blanchet
A M
AM
Collard-Dutilleul
V
V
Lalanne
J L
JL
Diu-Hercend
A
A
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D020170:Caspase 1; D020169:Caspases; D053471:Caspases, Initiator; D002478:Cells, Cultured; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003546:Cysteine Endopeptidases / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family; D011498:Protein Precursors / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014162:Transfection
D018076:DNA, Complementary; D007375:Interleukin-1; D011498:Protein Precursors; D011994:Recombinant Proteins; C093516:CASP4 protein, human; C099217:CASP5 protein, human; D020169:Caspases; D053471:Caspases, Initiator; D003546:Cysteine Endopeptidases; D020170:Caspase 1