RRC ID 46297
Author Chiorazzi M, Rui L, Yang Y, Ceribelli M, Tishbi N, Maurer CW, Ranuncolo SM, Zhao H, Xu W, Chan WC, Jaffe ES, Gascoyne RD, Campo E, Rosenwald A, Ott G, Delabie J, Rimsza LM, Shaham S, Staudt LM.
Title Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma.
Journal Proc Natl Acad Sci U S A
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.
Volume 110(10)
Pages 3943-8
Published 2013-3-5
DOI 10.1073/pnas.1217271110
PII 1217271110
PMID 23431138
PMC PMC3593917
MeSH Amino Acid Sequence Animals Apoptosis / physiology* Base Sequence Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Caspases / genetics Caspases / physiology Cell Line, Tumor Enzyme Activation F-Box Proteins / genetics F-Box Proteins / physiology* HEK293 Cells Humans Lymphoma / genetics Lymphoma / pathology* Lymphoma / physiopathology* Lymphoma, Large B-Cell, Diffuse / genetics Lymphoma, Large B-Cell, Diffuse / pathology Lymphoma, Large B-Cell, Diffuse / physiopathology Molecular Sequence Data Mutation, Missense Proto-Oncogene Proteins c-bcl-2 / genetics Proto-Oncogene Proteins c-bcl-2 / physiology RNA, Messenger / genetics RNA, Messenger / metabolism RNA, Neoplasm / genetics RNA, Neoplasm / metabolism Repressor Proteins / genetics Repressor Proteins / physiology Sequence Homology, Amino Acid
IF 9.412
Times Cited 36
C.elegans tm3719 tm2214