TNF-induced apoptosis involves activation of the ICE cysteine protease
(OMIM 147678). By using a yeast 2-hybrid screen to identify proteins that interact with the death domain of TNFR1, Hsu et al.
(1995) isolated cDNAs encoding a 34-kD protein that they designated TRADD (TNFR1-associated death domain protein).
Overexpression of TRADD led to 2 major TNF-induced responses, apoptosis and activation of NF-kappa-B. The predicted
312-amino acid TRADD protein contains a 111-amino acid death domain with sequence similarity to that of TNFR1. This
region of TRADD is capable of mediating TRADD oligomerization, TNFR1 interaction, stimulation of apoptosis, and
NF-kappa-B activation.
NCBI Summary:
The protein encoded by this gene is a death domain containing adaptor molecule that interacts with TNFRSF1A/TNFR1 and mediates programmed cell death signaling and NF-kappaB activation. This protein binds adaptor protein TRAF2, reduces the recruitment of inhibitor-of-apoptosis proteins (IAPs) by TRAF2, and thus suppresses TRAF2 mediated apoptosis. This protein can also interact with receptor TNFRSF6/FAS and adaptor protein FADD/MORT1, and is involved in the Fas-induced cell death pathway. Two alternatively spliced transcript variants encoding distinct isoforms have been reported.
General function
Comment
Cellular localization
Cytoplasmic
Comment
Ovarian function
Follicle atresia
Comment
Expression regulated by
Comment
Ovarian localization
Granulosa
Comment
TRADD is involved in apoptosis induction in granulosa cells during atresia in pig ovaries.
Author(s): Wada S, Manabe N, Inoue N, Nakayama M, Matsui T, Miyamoto H
Source: JOURNAL OF REPRODUCTION AND DEVELOPMENT
v. 48(#2) pp. 175-181 APR 2002
Previously, the authors histochemically demonstrated the expression of tumor necrosis
factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its receptors,
death receptor-4 (DR4), death receptor-5 (DR5) and decoy receptor-1 (DcR1) in
granulosa cells of porcine follicles. However, TRAIL can induce both cell
death and cell proliferation. In the present study, reverse transcription
polymerase chain reaction and in situ hybridization analyses revealed
increased mRNA expression of TNF receptor-associated death domain protein
(TRADD), which transmits the death signal from DR4 and/or DR5 to intracellular
apoptosis-signal transduction components, in granulosa cells was demonstrated
only in atretic follicles but not in healthy follicles. These findings
indicate that TRADD is involved in induction of apoptosis in granulosa cells,
and that the TRAIL-receptor system induces apoptosis in granulosa cells during
atresia in porcine ovaries.