The induction of the various cellular responses mediated by tumor necrosis factor (TNF; 191160) is initiated by its interaction with the TNFR1 (191190) and TNFR2 (191191) cell surface receptors. Rothe et al. (1994) used the yeast-based 2-hybrid system to detect mouse proteins that interact with the cytoplasmic domain of TNFR2. They identified and cloned 2 TNF receptor-associated factors which they termed TRAF1 (601711) and TRAF2. TRAF1 and TRAF2 share a C-terminal domain that the authors designated the TRAF domain. TRAF1 and TRAF2 can form both homo- and heterodimers. When expressed in yeast cells, a heterodimeric complex of TRAF1 and TRAF2 in which TRAF2 facilitates direct contact with the receptor was associated with the cytoplasmic domain of TNFR2.
NCBI Summary:
The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms a heterodimeric complex with TRAF1. This protein is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF1 interacts with the inhibitor-of-apoptosis proteins (IAPs), and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. BIRC2/c-IAP1, an apoptosis inhibitor possessing ubiquitin ligase activity, can unbiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.
General function
Comment
Cellular localization
Cytoplasmic, Plasma membrane
Comment
Ovarian function
Follicle atresia
Comment
Expression regulated by
Comment
Ovarian localization
Granulosa, Luteal cells
Comment
Nakayama M, et al 2003 reported changes in the Expression of Tumor Necrosis Factor (TNF) alpha, TNFalpha Receptor (TNFR) 2, and TNFR-Associated Factor 2 in Granulosa Cells During Atresia in Pig Ovaries.
Tumor necrosis factor (TNF) alpha can induce both cell death and cell proliferation and exerts its effects by binding to either TNF receptor (TNFR) 1 or 2. When TNFalpha-bound TNFR2 interacts with TNFR-associated factor 2 (TRAF2), expression of survival/antiapoptotic genes is up-regulated. In the present study the author determined the changes in localization of TNFalpha and TRAF2 and their mRNAs and the expression of TNFR2 in granulosa cells during follicular atresia in pig ovaries. In healthy follicles, intense signals for TNFalpha and TRAF2 and their mRNAs were demonstrated in the outer zone of the granulosa layer, where many proliferating cells and no apoptotic cells were observed. In atretic follicles, decreased or trace staining for TRAF2 and its mRNA and decreased expression of TNFR2 were observed in the granulosa layer, where many apoptotic cells were seen. These findings suggested that TNFalpha acts as a survival factor in granulosa cells during follicular atresia in pig ovaries.
Follicle stages
Antral, Corpus luteum
Comment
Expressions of tumor necrosis factor-a, its receptor I, II and receptor-associated factor 2 in the porcine corpus luteum during the estrous cycle and early pregnancy. Suzuki C 2013 et al.
We examined the gene and protein levels of tumor necrosis factor (TNF)-a, its receptors (types I and II, designated TNF-RI and TNF-RII, respectively), TNF receptor-associated factor 2 (TRAF2) and morphological features in the porcine corpus luteum (CL), on Days 13 and 17 (Day 0 = the last day of estrus) of the estrous cycle or of early pregnancy. Gene expression levels of TNF-a, TNF-RI, TNF-RII and TRAF2 were unaffected by the day or reproductive status. TNF-a concentration was significantly higher in the CL on Day 17 of pregnancy than on Day 13 of pregnancy and on day 17 of the estrous cycle. The TNF-RI protein level was significantly higher in the CL on Days 13 and 17 of pregnancy than those of the estrous cycle, significantly increasing on Day 17 compared with those on Day 13 in pregnancy. In relation to TNF-RII protein levels, although there were no change during pregnancy, there was a tendency (P?=?0.0524) to up-regulate as pregnancy proceeded. In estrous cycle, TNF-RII protein levels decreased significantly as luteolysis proceeded. TRAF2 protein level was significantly higher in the CL on Days 13 and 17 of pregnancy than during estrous. There were few apoptotic bodies in the CL between Days 13 and 17 of pregnancy than during esrous. There were few apoptotic bodies in the CL between Days 13 and 17 of pregnancy. The number of apoptotic bodies was much greater than the CL on Day 17 of the estrous than those of pregnancy. Thus, the TNF-a and TNF-RI and TNF-RII pathways including the TRAF2 protein, known to control of cell differentiation, tissue renewal and apoptosis, might participate in maintaining the porcine CL during early pregnancy.
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