Abstract
Bcl10 was identified as a candidate gene responsible for low grade B cell lymphomas of mucosa-associated lymphoid tissue. Overexpression of Bcl10 in cultured cells was reported to promote apoptosis, however, the mechanism of regulation of apoptosis mediated by Bcl10 has not been demonstrated. In the present study, we analysed the apoptosis signaling pathway mediated by Bcl10, focusing on phosphorylation of Bcl10 and the dynamic interaction with its binding partners during apoptosis. Previously, we have demonstrated that Bcl10 potentially interacts with the other apoptosis regulator, TNF receptor associated factor-2 (TRAF2) and inhibitor of apoptosis proteins (cIAPs). The present results showed that the complex formation of these molecules was regulated by phosphorylation of Bcl10, that is, phosphorylation of Bcl10 resulted in binding of Bcl10 to cIAPs and the dissociation of it from TRAF2. Moreover, hyperphosphorylation of Bcl10 enhanced apoptosis, suggesting that changes in the binding partners of Bcl10 were correlated to the promotion of apoptosis as mediated by Bcl10. Indeed, the mutant which was deleted from the binding site of Bcl10 for cIAPs, could not induce apoptosis. These findings indicate that Bcl10 is a mediator of apoptosis signaling, by switching over binding to cIAPs from TRAF2 through the events of Bcl10 phosphorylation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Arch RH, Gedrich RW, Thompson CB . 1998 Genes Dev. 12: 2821–2830
Bertin J, Guo Y, Wang L, Srinivasula SM, Jacobson MD, Poyet J-L, Merriam S, Du M-Q, Dyer MJS, Robinson KE, DiStefano PS, Alnemri ES . 2000 J. Biol. Chem. 275: 41082–41086
Bertoni F, Luminari S, Intini D, Carobbio S, Codegoni AM, Spataro V, Neri A . 1999 Ann. Oncol. 10: 1259
Cecconi F . 1999 Cell Death Differ. 6: 1087–1098
Chou JJ, Matsuo H, Duan H, Wagner G . 1998 Cell 94: 171–180
Du MQ, Peng H, Liu H, Hamoudi RA, Diss TC, Wills TG, Ye H, Dogan A, Wotherspoon AC, Dyer MJ, Isaacson PG . 2000 Blood 95: 3885–3890
Hoffman K, Bucher P, Tschopp J . 1997 Trends Biochem. Sci. 22: 155–156
Hofmann K . 1999 Cell. Mol. Life Sci. 55: 1113–1128
Kizaki H, Shimada H, Ishimura Y . 1989 J. Biochem. 105: 673–675
Koseki T, Inohara N, Chen S, Nunez G . 1998 Proc. Natl. Acad. Sci. USA 95: 5156–5160
Koseki T, Inohara N, Chen S, Carrio R, Merino J, Hottiger MO, Nabel GJ, Nunez G . 1999 J. Biol. Chem. 274: 9955–9961
Laouar A, Glesne D, Huberman E . 1999 J. Biol. Chem. 274: 23526–23534
McCarthy JV, Ni J, Dixit VM . 1998 J. Biol. Chem. 273: 16968–16975
Rothe M, Pan MG, Henzel WJ, Ayres TM, Goeddel DV . 1995 Cell 83: 1243–1252
Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC . 1997 EMBO J. 16: 6914–6925
Shu HB, Takeuchi M, Goeddel DV . 1996 Proc. Natl. Acad. Sci. USA 93: 13973–13978
Simms LA, Young J, Wicking C, Meltzer SJ, Jass JR, Leggett BA . 2000 Cell Death Differ. 7: 236–237
Takada Y, Hachiya M, Osawa Y, Hasegawa Y, Ando K, Kobayashi Y, Akashi M . 1999 J. Biol. Chem. 274: 28286–28292
Takahashi R, Deveraux Q, Tamm I, Welsh K, Assa MN, Salvesen GS, Reed JC . 1998 J. Biol. Chem. 273: 7787–7790
Thome M, Martinon F, Hofmann K, Rubio V, Steiner V, Schneider P, Mattmann C, Tschopp J . 1999 J. Biol. Chem. 274: 9962–9968
Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AJ . 1998 Science 281: 1680–1683
Willis TG, Jadayel DM, Du MQ, Peng H, Perry AR, Abdul RM, Price H, Karran L, Majekodunmi O, Wlodarska I, Pan L, Crook T, Hamoudi R, Isaacson PG, Dyer MJ . 1999 Cell 96: 35–45
Yamamoto H, Gil J, Schwartz SJ, Perucho M . 2000 Cell Death Differ. 7: 238–239
Yan M, Lee J, Schilbach S, Goddard A, Dixit V . 1999 J. Biol. Chem. 274: 10287–10292
Yeh W, Shahinian A, Speiser D, Kraunus J, Billia F, Wakeham A, de la Pompa JL, Ferrick D, Hum B, Iscove N, Ohashi P, Rothe M, Goeddel DV, Mak TW . 1997 Immunity 7: 715–725
Yoneda T, Imaizumi K, Maeda M, Yui D, Manabe T, Katayama T, Sato N, Gomi F, Morihara T, Mori Y, Miyoshi K, Hitomi J, Ugawa S, Yamada S, Okabe M, Tohyama M . 2000 J. Biol. Chem. 275: 11114–11120
Zhang Q, Siebert R, Yan M, Hinzmann B, Cui X, Xue L, Rakestraw KM, Naeve CW, Beckmann G, Weisenburger DD, Sanger WG, Nowotny H, Vesely M, Callet BE, Salles G, Dixit VM, Rosenthal A, Schlegelberger B, Morris SW . 1999 Nat. Genet. 22: 63–68
Acknowledgements
We would like to thank Akemi Arakawa for technical assistance, and Dr Ryosuke Takahashi (Brain Science Research Center, RIKEN) for providing the cIAPs cDNA vectors. This work was supported by grants from CREST of Japan Science and Technology Corporation (JST).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yui, D., Yoneda, T., Oono, K. et al. Interchangeable binding of Bcl10 to TRAF2 and cIAPs regulates apoptosis signaling. Oncogene 20, 4317–4323 (2001). https://doi.org/10.1038/sj.onc.1204576
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204576
Keywords
This article is cited by
-
The CARMA1 signalosome links the signalling machinery of adaptive and innate immunity in lymphocytes
Nature Reviews Immunology (2006)
-
NF-κB/Rel-mediated regulation of apoptosis in hematologic malignancies and normal hematopoietic progenitors
Leukemia (2004)
-
Defective development and function of Bcl10-deficient follicular, marginal zone and B1 B cells
Nature Immunology (2003)