Disassembly of the JIP1/JNK Molecular Scaffold by Caspase-3-mediated Cleavage of JIP1 During Apoptosis

Overview

Journal Exp Cell Res

Specialty Cell Biology

Date 2011 Jan 18

PMID 21237154

Citations 8

Authors

Mahesh Vaishnav

Marion MacFarlane

Martin Dickens

Affiliations

Soon will be listed here.

Abstract

We report here the cleavage of the c-Jun N-terminal Kinase (JNK) pathway scaffold protein, JNK Interacting Protein-1 (JIP1), by caspases during both Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) and staurosporine-induced apoptosis in HeLa cells. During the initiation of apoptosis, maximal JNK activation is observed when JIP1 is intact, whereas cleavage of JIP1 correlates with JNK inactivation and progression of apoptosis. JIP1 is cleaved by caspase-3 at two sites, leading to disassembly of the JIP1/JNK complex. Inhibition of JIP1 cleavage by the caspase-3 inhibitor DEVD.fmk inhibits this disassembly, and is accompanied by sustained JNK activation. These data suggest that TRAIL and staurosporine induce JNK activation in a caspase-3-independent manner and that caspase-3-mediated JIP1 cleavage plays a role in JNK inactivation via scaffold disassembly during the execution phase of apoptosis. Caspase-mediated cleavage of JIP scaffold proteins may therefore represent an important mechanism for modulation of JNK signalling during apoptotic cell death.

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References

Ashkenazi A . Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer. 2002; 2(6):420-30. DOI: 10.1038/nrc821. View

Bratton S, MacFarlane M, Cain K, Cohen G . Protein complexes activate distinct caspase cascades in death receptor and stress-induced apoptosis. Exp Cell Res. 2000; 256(1):27-33. DOI: 10.1006/excr.2000.4835. View

Kyriakis J, Avruch J . Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 2001; 81(2):807-69. DOI: 10.1152/physrev.2001.81.2.807. View

Arends M, Wyllie A . Apoptosis: mechanisms and roles in pathology. Int Rev Exp Pathol. 1991; 32:223-54. DOI: 10.1016/b978-0-12-364932-4.50010-1. View

Sabapathy K, Kallunki T, David J, GRAEF I, Karin M, Wagner E . c-Jun NH2-terminal kinase (JNK)1 and JNK2 have similar and stage-dependent roles in regulating T cell apoptosis and proliferation. J Exp Med. 2001; 193(3):317-28. PMC: 2195924. DOI: 10.1084/jem.193.3.317. View

Bonny C, NICOD P, Waeber G . IB1, a JIP-1-related nuclear protein present in insulin-secreting cells. J Biol Chem. 1998; 273(4):1843-6. DOI: 10.1074/jbc.273.4.1843. View

Xia Z, Dickens M, Raingeaud J, Davis R, Greenberg M . Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. 1995; 270(5240):1326-31. DOI: 10.1126/science.270.5240.1326. View

Lee C, Onesime D, Damodara Reddy C, Dhanasekaran N, Reddy E . JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors. Proc Natl Acad Sci U S A. 2002; 99(22):14189-94. PMC: 137859. DOI: 10.1073/pnas.232310199. View

Sabapathy K, Jochum W, Hochedlinger K, Chang L, Karin M, Wagner E . Defective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2. Mech Dev. 1999; 89(1-2):115-24. DOI: 10.1016/s0925-4773(99)00213-0. View

10.

Martinon F, Holler N, Richard C, Tschopp J . Activation of a pro-apoptotic amplification loop through inhibition of NF-kappaB-dependent survival signals by caspase-mediated inactivation of RIP. FEBS Lett. 2000; 468(2-3):134-6. DOI: 10.1016/s0014-5793(00)01212-6. View

11.

Sun X, Butterworth M, MacFarlane M, Dubiel W, Ciechanover A, Cohen G . Caspase activation inhibits proteasome function during apoptosis. Mol Cell. 2004; 14(1):81-93. DOI: 10.1016/s1097-2765(04)00156-x. View

12.

Wen L, Fahrni J, Troie S, Guan J, Orth K, Rosen G . Cleavage of focal adhesion kinase by caspases during apoptosis. J Biol Chem. 1997; 272(41):26056-61. DOI: 10.1074/jbc.272.41.26056. View

13.

Widmann C, Gerwins P, Johnson N, Jarpe M, Johnson G . MEK kinase 1, a substrate for DEVD-directed caspases, is involved in genotoxin-induced apoptosis. Mol Cell Biol. 1998; 18(4):2416-29. PMC: 121502. DOI: 10.1128/MCB.18.4.2416. View

14.

Deng Y, Ren X, Yang L, Lin Y, Wu X . A JNK-dependent pathway is required for TNFalpha-induced apoptosis. Cell. 2003; 115(1):61-70. DOI: 10.1016/s0092-8674(03)00757-8. View

15.

Lamb J, Ventura J, Hess P, Flavell R, Davis R . JunD mediates survival signaling by the JNK signal transduction pathway. Mol Cell. 2003; 11(6):1479-89. DOI: 10.1016/s1097-2765(03)00203-x. View

16.

MacFarlane M, Cohen G, Dickens M . JNK (c-Jun N-terminal kinase) and p38 activation in receptor-mediated and chemically-induced apoptosis of T-cells: differential requirements for caspase activation. Biochem J. 2000; 348 Pt 1:93-101. PMC: 1221040. View

17.

Yasuda J, Whitmarsh A, Cavanagh J, Sharma M, Davis R . The JIP group of mitogen-activated protein kinase scaffold proteins. Mol Cell Biol. 1999; 19(10):7245-54. PMC: 84717. DOI: 10.1128/MCB.19.10.7245. View

18.

Whitmarsh A, Cavanagh J, Tournier C, Yasuda J, Davis R . A mammalian scaffold complex that selectively mediates MAP kinase activation. Science. 1998; 281(5383):1671-4. DOI: 10.1126/science.281.5383.1671. View

19.

Hess P, Pihan G, Sawyers C, Flavell R, Davis R . Survival signaling mediated by c-Jun NH(2)-terminal kinase in transformed B lymphoblasts. Nat Genet. 2002; 32(1):201-5. DOI: 10.1038/ng946. View

20.

Kim B, Ryu S, Song B . JNK- and p38 kinase-mediated phosphorylation of Bax leads to its activation and mitochondrial translocation and to apoptosis of human hepatoma HepG2 cells. J Biol Chem. 2006; 281(30):21256-21265. DOI: 10.1074/jbc.M510644200. View