Activation of caspases-8 and-10 by FLIPL

被引:187
作者
Boatright, KM
Deis, C
Denault, JB
Sutherlin, DP
Salvesen, GS
机构
[1] Burnham Inst, Program Apoptosis & Cell Death Res, La Jolla, CA 92037 USA
[2] Univ Calif San Diego, Grad Program Mol Pathol, La Jolla, CA 92037 USA
[3] Genentech Inc, Dept Med Chem, San Francisco, CA 94080 USA
关键词
apoptosis; caspase-8; FLIPL (FLICE-like inhibitory protein); protease; zymogen;
D O I
10.1042/BJ20040809
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The first step in caspase activation is transition of the latent zymogen to an active form. For the initiator caspases, this occurs through dimerization of monomeric zymogens at an activating complex. Recent studies have suggested that FLIPL [FLICE-like inhibitory protein, long form; FLICE is FADD (Fas-associated death domain protein)-like interleukin-1beta-converting enzyme], previously thought to act solely as an inhibitor of caspase-8 activation, can under certain circumstances function to enhance caspase activation. Using an in vitro induced-proximity assay, we demonstrate that activation of caspases-8 and -10 occurs independently of cleavage of either the caspase or FLIPL. FLIPL activates caspase-8 by forming heterodimeric enzyme molecules with substrate specificity and catalytic activity indistinguishable from those of caspase-8 homodimers. Significantly, the barrier for heterodimer formation is lower than that for homodimer formation, suggesting that FLIPL is a more potent activator of caspase-8 than is caspase-8 itself.
引用
收藏
页码:651 / 657
页数:7
相关论文
共 31 条
  • [1] Human ICE/CED-3 protease nomenclature
    Alnemri, ES
    Livingston, DJ
    Nicholson, DW
    Salvesen, G
    Thornberry, NA
    Wong, WW
    Yuan, JY
    [J]. CELL, 1996, 87 (02) : 171 - 171
  • [2] Death receptors: Signaling and modulation
    Ashkenazi, A
    Dixit, VM
    [J]. SCIENCE, 1998, 281 (5381) : 1305 - 1308
  • [3] Mechanisms of caspase activation
    Boatright, KM
    Salvesen, GS
    [J]. CURRENT OPINION IN CELL BIOLOGY, 2003, 15 (06) : 725 - 731
  • [4] A unified model for apical caspase activation
    Boatright, KM
    Renatus, M
    Scott, FL
    Sperandio, S
    Shin, H
    Pedersen, IM
    Ricci, JE
    Edris, WA
    Sutherlin, DP
    Green, DR
    Salvesen, GS
    [J]. MOLECULAR CELL, 2003, 11 (02) : 529 - 541
  • [5] Crystal structure of a procaspase-7 zymogen: Mechanisms of activation and substrate binding
    Chai, JJ
    Wu, Q
    Shiozaki, E
    Srinivasula, SM
    Alnemri, ES
    Shi, YG
    [J]. CELL, 2001, 107 (03) : 399 - 407
  • [6] c-FLIPL is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis
    Chang, DW
    Xing, Z
    Pan, Y
    Algeciras-Schimnich, A
    Barnhart, BC
    Yaish-Ohad, S
    Peter, ME
    Yang, XL
    [J]. EMBO JOURNAL, 2002, 21 (14) : 3704 - 3714
  • [7] Interdimer processing mechanism of procaspase-8 activation
    Chang, DW
    Xing, Z
    Capacio, VL
    Peter, ME
    Yang, XL
    [J]. EMBO JOURNAL, 2003, 22 (16) : 4132 - 4142
  • [8] Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency
    Chun, HJ
    Zheng, LX
    Ahmad, M
    Wang, J
    Speirs, CK
    Siegel, RM
    Dale, MK
    Puck, J
    Davis, J
    Hall, CG
    Skoda-Smith, S
    Atkinson, TP
    Straus, SE
    Lenardo, MJ
    [J]. NATURE, 2002, 419 (6905) : 395 - 399
  • [9] X-linked IAP is a direct inhibitor of cell-death proteases
    Deveraux, QL
    Takahashi, R
    Salvesen, GS
    Reed, JC
    [J]. NATURE, 1997, 388 (6639) : 300 - 304
  • [10] Insights into the regulatory mechanism for caspase-8 activation
    Donepudi, M
    Mac Sweeney, A
    Briand, C
    Grütter, MG
    [J]. MOLECULAR CELL, 2003, 11 (02) : 543 - 549