Apo-3, a new member of the tumor necrosis factor receptor family, contains a death domain and activates apoptosis and NF-kappa B.
Curr Biol
; 6(12): 1669-76, 1996 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-8994832
ABSTRACT
BACKGROUND:
Two receptors that contain the so-called "death domain' have been described to date tumor necrosis factor receptor 1 (TNFR1) and Fas/Apo-1 (CD95); both belong to the TNFR gene family. The death domain of TNFR1 mediates the activation of programmed cell death (apoptosis) and of the transcription factor NF-kappa B, whereas the death domain of CD95 only appears to activate apoptosis.RESULTS:
We have identified an additional member of the TNFR family, which we have named Apo-3. Apo-3 is a transmembrane protein of approximately 47 kDa that has similarity of members of the TNFR family in its extracellular, cysteine-rich domains. In addition, Apo-3 resembles TNFR1 and CD95 in that it contains a cytoplasmic death domain. The Apo-3 gene mapped to human chromosome 1p36.3, and Apo-3 mRNA was detected in several human tissues, including spleen, thymus, peripheral blood lymphocytes, small intestine and colon. Ectopic expression of Apo-3 in HEK293 or HeLa cells induced marked apoptosis. CrmA, a poxvirus inhibitor of Ced-3-like proteases which blocks death signaling by TNFR1 and CD95, inhibited Apo-3-induced apoptosis. Ectopic expression of Apo-3 also induced the activation of NF-kappa B. Apo-3 did not specifically bind to the Apo-2 ligand, suggesting the existence of a distinct ligand for Apo-3.CONCLUSIONS:
These results identify Apo-3 as a third member of the TNFR family that activates apoptosis, and suggest that Apo-3, TNFR1 and CD95 engage a common apoptotic cell-death machinery. Apo-3 resembles TNFR1 because it can stimulate NF-kappa B activity and regulate apoptosis. Apo-3 mRNA is expressed in various tissues, consistent with the possibility that this receptor may regulate multiple signaling functions.
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Base de datos:
MEDLINE
Asunto principal:
Proteínas Virales
/
Cromosomas Humanos Par 1
/
FN-kappa B
/
Apoptosis
/
Receptores del Factor de Necrosis Tumoral
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Curr Biol
Asunto de la revista:
BIOLOGIA
Año:
1996
Tipo del documento:
Article