A novel human protease similar to the interleukin-1 beta converting enzyme induces apoptosis in transfected cells.
We have identified a novel cDNA encoding a protein (named TX) with > 50% overall sequence identity with the interleukin-1 beta converting enzyme (ICE) and approximately 30% sequence identity with the ICE homologs NEDD-2/ICH-1L and CED-3. A computer homology model of TX was constructed based on the X-ray coordinates of the ICE crystal recently published. This model suggests that TX is a cysteine protease, with the P1 aspartic acid substrate specificity retained. Transfection experiments demonstrate that TX is a protease which is able to cleave itself and the p30 ICE precursor, but not to generate mature IL-1 beta from pro-IL-1 beta. In addition, this protein induces apoptosis in transfected COS cells. TX therefore delineates a new member of the growing Ice/ced-3 gene family coding for proteases with cytokine processing activity or involved in programmed cell death.
Faucheu
C
C
Roussel-Uclaf, Romainville, France.
Diu
A
A
Chan
A W
AW
Blanchet
A M
AM
Miossec
C
C
Hervé
F
F
Collard-Dutilleul
V
V
Gu
Y
Y
Aldape
R A
RA
Lippke
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D020170:Caspase 1; D020169:Caspases; D053471:Caspases, Initiator; D002460:Cell Line; D003001:Cloning, Molecular; D003198:Computer Simulation; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D018076:DNA, Complementary; D012333:RNA, Messenger; D010450:Endopeptidases; C093516:CASP4 protein, human; D020169:Caspases; D053471:Caspases, Initiator; D003546:Cysteine Endopeptidases; D020170:Caspase 1