Title | Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Chiorazzi M, Rui L, Yang Y, Ceribelli M, Tishbi N, Maurer CW, Ranuncolo SM, Zhao H, Xu W, Chan W-CC, Jaffe ES, Gascoyne RD, Campo E, Rosenwald A, Ott G, Delabie J, Rimsza LM, Shaham S, Staudt LM |
Journal | Proc Natl Acad Sci U S A |
Volume | 110 |
Issue | 10 |
Pagination | 3943-8 |
Date Published | 2013 Mar 05 |
ISSN | 1091-6490 |
Keywords | Amino Acid Sequence, Animals, Apoptosis, Base Sequence, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Caspases, Cell Line, Tumor, Enzyme Activation, F-Box Proteins, HEK293 Cells, Humans, Lymphoma, Lymphoma, Large B-Cell, Diffuse, Molecular Sequence Data, Mutation, Missense, Proto-Oncogene Proteins c-bcl-2, Repressor Proteins, RNA, Messenger, RNA, Neoplasm, Sequence Homology, Amino Acid |
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. |
DOI | 10.1073/pnas.1217271110 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 23431138 |
PubMed Central ID | PMC3593917 |
Grant List | U01 CA114778 / CA / NCI NIH HHS / United States R01HD042680 / HD / NICHD NIH HHS / United States GM07739 / GM / NIGMS NIH HHS / United States F30AG035484 / AG / NIA NIH HHS / United States R01 HD042680 / HD / NICHD NIH HHS / United States UO1-CA 114778 / CA / NCI NIH HHS / United States R01NS081490 / NS / NINDS NIH HHS / United States / / Intramural NIH HHS / United States R01 NS081490 / NS / NINDS NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States F30 AG035484 / AG / NIA NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:11pm