The Ret finger protein induces apoptosis via its RING finger-B box-coiled-coil motif.
The Ret finger protein (RFP) is a member of the tripartite motif family, which is characterized by a conserved RING finger, a B-box, and a coiled-coil domain (together called RBCC). Although RFP is known to become oncogenic when its RBCC moiety is connected to a tyrosine kinase domain by DNA rearrangement, its biological function is not well defined. Here we show that ectopic expression of RFP in human embryonic kidney 293 cells causes extensive apoptosis, as assessed by multiple criteria. RFP expression activates Jun N-terminal kinase and p38 kinase and also increases caspase-3-like activity. However, RFP failed to release cytochrome c and, therefore, to increase caspase-9-like activity. RFP-induced apoptosis could be blocked by the caspase-8 inhibitor crmA and dominant negative ASK1 but not by Bcl-2. These results reveal a novel RFP death pathway that recruits mitogen-activated protein kinase and caspases independently of mitochondrial events. Domain mapping showed that the intact RBCC moiety is necessary for the pro-apoptotic function of RFP. Moreover, expression of the RBCC moiety further potentiated the pro-apoptotic activity and resulted in a 7-fold increase of caspase activation compared with that induced by full-length RFP. This suggests that a large number of tripartite motif family members sharing the RBCC moiety may participate in the control of cell survival.
Dho
So Hee
SH
Laboratory of Functional Proteomics, Korea Research Institute of Bioscience and Biotechnology, Taejon 305-333, Korea.
Kwon
Ki-Sun
KS
D020816:Amino Acid Motifs; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases; D000070584:Tripartite Motif Proteins
D020169:Caspases; D004268:DNA-Binding Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009687:Nuclear Proteins; D048051:p38 Mitogen-Activated Protein Kinases; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins