| First Author | Stegh AH | Year | 1998 |
| Journal | EMBO J | Volume | 17 |
| Issue | 20 | Pages | 5974-86 |
| PubMed ID | 9774341 | Mgi Jnum | J:50530 |
| Mgi Id | MGI:1306907 | Doi | 10.1093/emboj/17.20.5974 |
| Citation | Stegh AH, et al. (1998) DEDD, a novel death effector domain-containing protein, targeted to the nucleolus. EMBO J 17(20):5974-86 |
| abstractText | The CD95 signaling pathway comprises proteins that contain one or two death effector domains (DED), such as FADD/Mort1 or caspase-8. Here we describe a novel 37 kDa protein, DEDD, that contains an N-terminal DED. DEDD is highly conserved between human and mouse (98. 7% identity) and is ubiquitously expressed. Overexpression of DEDD in 293T cells induced weak apoptosis, mainly through its DED by which it interacts with FADD and caspase-8. Endogenous DEDD was found in the cytoplasm and translocated into the nucleus upon stimulation of CD95. Immunocytological studies revealed that overexpressed DEDD directly translocated into the nucleus, where it co-localizes in the nucleolus with UBF, a basal factor required for RNA polymerase I transcription. Consistent with its nuclear localization, DEDD contains two nuclear localization signals and the C-terminal part shares sequence homology with histones. Recombinant DEDD binds to both DNA and reconstituted mononucleosomes and inhibits transcription in a reconstituted in vitro system. The results suggest that DEDD is a final target of a chain of events by which the CD95-induced apoptotic signal is transferred into the nucleolus to shut off cellular biosynthetic activities. |
