Interleukin P-converting enzyme

Hara H., Friedlander, R. M., Gagliardini, V., Ayata, C., Fink, K., Huang, Z., et al. (1997) Inhibition of Interleukin 1 p converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage. Proc. Natl. Acad. Sci. USA 94, 2007-2012. 

Takeda M, Kobayashi M, Shirato I, Osaki T, Endou FI. Cisplatin-induced apoptosis of immortalized mouse proximal tubule cells is mediated by interleukin-1 p converting enzyme (ICE) family of proteases but inhibited by overexpression of Bcl-2. Arch Toxicol 1997 71 612-621. 

SCH 58450 inhibited recombinant human FPTase (IC50 = 29 pM) and was 25-fold selective over GGPTase I (IC50 = 740 pM) [130]. EP-1507-2 was also reported to inhibit interleukin-1 p converting enzyme with an IC50 value of 0.42 pM [131], however, the mechanism of inhibition was not reported. 

FLICE Fas-associated death domain-like interleukin 1 P-converting enzyme... 

Geng, Y.J., and Libby, P., 1995, Evidence for apoptosis in advanced human atheroma. Colocalization with interleukin-1 beta-converting enzyme. Am. J. Pathol. 147 251-266. 

Friedlander RM, Gagliardini V, Roteilo RJ, Yuan J. Functional role of interleukin 1 p (IL-1 P) in IL-1 p-converting enzyme-mediated apoptosis. J Exp Med 1996 184 717-24. 

Komiyama, T., Ray, C.A., Pickup, D.J., Howard, A.D., Thornberry, N.A., Peterson, E.P. and Salvesen, G. (1994) Inhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition./. Biol. Chem. 269 19331-19337. 

Oshikawa, K., Shi, F., Rakhmilevich, A.L., Sondel, P.M., Mahvi, D.M. and Yang, N.-S. (1999) Synergistic inhibition of tumor growth in a murine mammary adenocarcinoma model by combinational gene therapy using interleukin-12, pro-interleukin-18 andIL-1 -converting enzyme cDNA. Proc. Natl. Acad. Sci. USA, 96, 13351-13356. 

Interleukin-lp converting enzyme (ICE, which converts the M, 33,000 protease form of interleukin-ip to the active M, 17,500 form by cleaving after Asp residues) and other members of the ICE-like family of proteases appear to play a significant role in A. For example, expresrion of CrmA protein (a protease inhibitor that inhibits ICE) potently blocks the A. induced by stimulation of Fas or TNF-1, implying that ICE-type proteases are involved in these suicide pathways. Proteins identified as early targets or death substrates associated with the onset of A. are poly(ADP-ribose) polymerase, lamin Bl, a-fodrin, topoisomerase I, p-actin, and the Af, 70,000 compo nent of the U1 small ribonucleoprotein (Ul-70kD). 

---