title: Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma.
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.
authors: Laboratory of Developmental Genetics, The Rockefeller University, New York, NY 10065, USA.
authors: Michael
authors: M
authors: Chiorazzi
authors: Lixin
authors: L
authors: Rui
authors: Yandan
authors: Y
authors: Yang
authors: Michele
authors: M
authors: Ceribelli
authors: Nima
authors: N
authors: Tishbi
authors: Carine W
authors: CW
authors: Maurer
authors: Stella M
authors: SM
authors: Ranuncolo
authors: Hong
authors: H
authors: Zhao
authors: Weihong
authors: W
authors: Xu
authors: Wing-Chung C
authors: WC
authors: Chan
authors: Elaine S
authors: ES
authors: Jaffe
authors: Randy D
authors: RD
authors: Gascoyne
authors: Elias
authors: E
authors: Campo
authors: Andreas
authors: A
authors: Rosenwald
authors: German
authors: G
authors: Ott
authors: Jan
authors: J
authors: Delabie
authors: Lisa M
authors: LM
authors: Rimsza
authors: Shai
authors: S
authors: Shaham
authors: Louis M
authors: LM
authors: Staudt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D020169:Caspases / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D044783:F-Box Proteins / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D008223:Lymphoma / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D017386:Sequence Homology, Amino Acid
chemical_list: D029742:Caenorhabditis elegans Proteins; C519094:DRE-1 protein, C elegans; C112486:EGL-1 protein, C elegans; D044783:F-Box Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012097:Repressor Proteins; D020169:Caspases; C089223:ced-3 protein, C elegans