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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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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.
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.
Chicago author-date
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.
Chicago author-date (all authors)
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.
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.
IEEE
[1]
L. Vande Walle et al., “The mitochondrial serine protease HtrA2/Omi cleaves RIP1 during apoptosis of Ba/F3 cells induced by growth factor withdrawal,” CELL RESEARCH, vol. 20, no. 4, pp. 421–433, 2010.
@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}},
  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}},
  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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