Related F-box proteins control cell death in caenorhabditis elegans and human lymphoma

Michael Chiorazzi, Lixin Rui, Yandan Yang, Michele Ceribelli, Nima Tishbi, Carine W. Maurer, Stella M. Ranuncolo, Hong Zhao, Weihong Xu, Wing Chung C. Chan, Elaine S. Jaffe, Randy D. Gascoyne, Elias Campo, Andreas Rosenwald, German Ott, Jan Delabie, Lisa M. Rimsza, Shai Shaham, Louis M. Staudt

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Cell death is a common metazoan cell fate, and its inactivation is central to human malignancy. In Caenorhabditis elegans, apoptotic cell death occurs via the activation of the caspase CED-3 following binding of the EGL-1/BH3-only protein to the antiapoptotic CED-9/ BCL2 protein. Here we report a major alternative mechanism for caspase activation in vivo involving the F-box protein DRE-1. DRE-1 functions in parallel to EGL-1, requires CED-9 for activity, and binds to CED-9, suggesting that DRE-1 promotes apoptosis by inactivating CED-9. FBXO10, a human protein related to DRE-1, binds BCL2 and promotes its degradation, thereby initiating cell death. Moreover, some human diffuse large B-cell lymphomas have inactivating mutations in FBXO10 or express FBXO10 at low levels. Our results suggest that DRE-1/FBXO10 is a conserved regulator of apoptosis.

Original languageEnglish (US)
Pages (from-to)3943-3948
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number10
DOIs
StatePublished - Mar 5 2013

Keywords

  • Cancer
  • Ubiquitin

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Related F-box proteins control cell death in caenorhabditis elegans and human lymphoma'. Together they form a unique fingerprint.

  • Cite this

    Chiorazzi, M., Rui, L., Yang, Y., Ceribelli, M., Tishbi, N., Maurer, C. W., Ranuncolo, S. M., Zhao, H., Xu, W., Chan, W. C. C., Jaffe, E. S., Gascoyne, R. D., Campo, E., Rosenwald, A., Ott, G., Delabie, J., Rimsza, L. M., Shaham, S., & Staudt, L. M. (2013). Related F-box proteins control cell death in caenorhabditis elegans and human lymphoma. Proceedings of the National Academy of Sciences of the United States of America, 110(10), 3943-3948. https://doi.org/10.1073/pnas.1217271110