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The mitochondrial serine protease HtrA2/Omi cleaves RIP1 during apoptosis of Ba/F3 cells induced by growth factor withdrawal

(2010) CELL RESEARCH. 20(4). p.421-433
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Abstract
Interleukin-3 (IL-3) deprivation of the mouse pro-B cell line Ba/F3 induces cell death that is abrogated by B-cell lymphoma 2 (Bcl-2) overexpression, but remains unaffected by the pan-caspase inhibitor carbobenzoxy-valyl-analyl-aspartyl-[O-methyl]-fluoromethylketone (zVAD-fmk). IL-3 withdrawal causes receptor-interacting protein (RIP)1 cleavage into C-terminal fragments of 30 and 25 kDa, and only cleavage leading to the former was prevented by zVAD-fmk. siRNA experiments demonstrated that generation of the 25-kDa fragment was due to a Bcl-2-modulated release of the mitochondrial serine protease high temperature requirement protein A2 (HtrA2)/Omi. Accordingly, recombinant HtrA2/Omi efficiently cleaved mouse RIP1 in vitro, generating fragments matching those observed in IL-3-deprived Ba/F3 cells. The HtrA2/Omi cleavage site in mouse RIP1 was mapped to the intermediate domain and the corresponding N- and C-terminal fragments were impaired in their ability to activate nuclear factor-#B, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. Interestingly, knockdown of HtrA2/Omi afforded pro-tection against IL-3 withdrawal-induced death in the presence of zVAD-fmk, demonstrating a role for HtrA2/Omi in caspase-independent cell death during growth factor withdrawal by cleaving RIP1.
Keywords
ACTIVATION, HEMATOPOIETIC-CELLS, TUMOR-NECROSIS-FACTOR, DEATH, SURVIVAL SIGNALS, apoptosis, IL-3, Ba/F3, RIP1, HtrA2/Omi, OMI/HTRA2, CASPASE ACTIVITY, DOMAIN KINASE RIP, INTERLEUKIN-3, NF-KAPPA-B

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Citation

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Chicago
Vande Walle, Lieselotte, Ellen Wirawan, Mohamed Lamkanfi, Nele Festjens, Jelle Verspurten, Xavier Saelens, Tom Vanden Berghe, and Peter Vandenabeele. 2010. “The Mitochondrial Serine Protease HtrA2/Omi Cleaves RIP1 During Apoptosis of Ba/F3 Cells Induced by Growth Factor Withdrawal.” Cell Research 20 (4): 421–433.
APA
Vande Walle, L., Wirawan, E., Lamkanfi, M., Festjens, N., Verspurten, J., Saelens, X., Vanden Berghe, T., et al. (2010). The mitochondrial serine protease HtrA2/Omi cleaves RIP1 during apoptosis of Ba/F3 cells induced by growth factor withdrawal. CELL RESEARCH, 20(4), 421–433.
Vancouver
1.
Vande Walle L, Wirawan E, Lamkanfi M, Festjens N, Verspurten J, Saelens X, et al. The mitochondrial serine protease HtrA2/Omi cleaves RIP1 during apoptosis of Ba/F3 cells induced by growth factor withdrawal. CELL RESEARCH. 2010;20(4):421–33.
MLA
Vande Walle, Lieselotte et al. “The Mitochondrial Serine Protease HtrA2/Omi Cleaves RIP1 During Apoptosis of Ba/F3 Cells Induced by Growth Factor Withdrawal.” CELL RESEARCH 20.4 (2010): 421–433. Print.
@article{940390,
  abstract     = {Interleukin-3 (IL-3) deprivation of the mouse pro-B cell line Ba/F3 induces cell death that is abrogated by B-cell lymphoma 2 (Bcl-2) overexpression, but remains unaffected by the pan-caspase inhibitor carbobenzoxy-valyl-analyl-aspartyl-[O-methyl]-fluoromethylketone (zVAD-fmk). IL-3 withdrawal causes receptor-interacting protein (RIP)1 cleavage into C-terminal fragments of 30 and 25 kDa, and only cleavage leading to the former was prevented by zVAD-fmk. siRNA experiments demonstrated that generation of the 25-kDa fragment was due to a Bcl-2-modulated release of the mitochondrial serine protease high temperature requirement protein A2 (HtrA2)/Omi. Accordingly, recombinant HtrA2/Omi efficiently cleaved mouse RIP1 in vitro, generating fragments matching those observed in IL-3-deprived Ba/F3 cells. The HtrA2/Omi cleavage site in mouse RIP1 was mapped to the intermediate domain and the corresponding N- and C-terminal fragments were impaired in their ability to activate nuclear factor-\#B, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. Interestingly, knockdown of HtrA2/Omi afforded pro-tection against IL-3 withdrawal-induced death in the presence of zVAD-fmk, demonstrating a role for HtrA2/Omi in caspase-independent cell death during growth factor withdrawal by cleaving RIP1.},
  author       = {Vande Walle, Lieselotte and Wirawan, Ellen and Lamkanfi, Mohamed and Festjens, Nele and Verspurten, Jelle and Saelens, Xavier and Vanden Berghe, Tom and Vandenabeele, Peter},
  issn         = {1001-0602},
  journal      = {CELL RESEARCH},
  language     = {eng},
  number       = {4},
  pages        = {421--433},
  title        = {The mitochondrial serine protease HtrA2/Omi cleaves RIP1 during apoptosis of Ba/F3 cells induced by growth factor withdrawal},
  url          = {http://dx.doi.org/10.1038/cr.2010.18},
  volume       = {20},
  year         = {2010},
}

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