NCBI Summary:
The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein is one of the major receptors for the tumor necrosis factor-alpha. This receptor can activate NF-kappaB, mediate apoptosis, and function as a regulator of inflammation. Antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRADD and TRAF2 have been shown to interact with this receptor, and thus play regulatory roles in the signal transduction mediated by the receptor. Germline mutations of the extracellular domains of this receptor were found to be associated with the autosomal dominant periodic fever syndrome. The impaired receptor clearance is thought to be a mechanism of the disease.
Genes whose expression is detected by cDNA array hybridization: GDP/GTP exchangers, GTPase stimulators and inhibitors, apoptosis Rozenn Dalbi?Tran and Pascal Mermilloda Tumor Necrosis Factor (TNF) Receptor Type 2 Is an Important Mediator of TNF alpha Function in the Mouse Ovary. Greenfeld CR et al. It is believed that a finite pool of primordial follicles is established during embryonic and neonatal life. At birth, the mouse ovary consists of clusters of interconnected oocytes surrounded by pregranulosa cells. Shortly after birth, these structures, termed germ cell cysts or nests (GCN), breakdown to facilitate primordial follicle formation. Tumor necrosis factor alpha (TNF) is a widely expressed protein with myriad functions. TNF is expressed in the ovary and may regulate GCN breakdown in rats. We investigated whether it participates in GCN breakdown and follicle formation in mice, utilizing an in vitro ovary culture system, as well as mutant animal models. We found that TNF and both receptors (TNFRSF1A and TNFRSF1B) are expressed in neonatal mouse ovaries, and that TNF promotes oocyte death in neonatal ovaries in vitro. However, deletion of either receptor did not effect follicle endowment, suggesting that TNF does not regulate GCN breakdown in vivo. Tnfrsf1b deletion led to an apparent acceleration of follicular growth, and a concomitant expansion of the primordial follicle population. This expansion of the primordial follicle population does not appear to be due to decreased primordial follicle atresia, though this cannot be ruled out completely. This study demonstrates that mouse oocytes express both TNF receptors and are sensitive to TNF-induced death. Additionally, TNFRSF1B is demonstrated to be an important mediator of TNF function in the mouse ovary, and an important regulator of folliculogenesis.
Expression regulated by
Comment
Ovarian localization
Granulosa
Comment
Tumor necrosis factor {alpha} (TNF) increases granulosa cell proliferation: dependence on c-Jun and TNF receptor type-1.
Son DS, et al .
Tumor necrosis factor alpha (TNF) has significant in vitro effects on steroidogenesis and folliculogenesis and reproductive alterations occur in TNF receptor type 1 (TNFR1) knockout mice. The present study investigated the effect of in vitro TNF on granulosa cell proliferation from immature mice at 28 days of age, with emphasis on intracellular signaling that regulates granulosa cell proliferation. TNF dose dependently increased granulosa cell proliferation and the proto-oncogene c-Jun protein. However, other Jun family members such as JunD was expressed constitutively and JunB was not expressed. In vitro TNF did not increase c-Jun and proliferation in granulosa cells from TNFR1 knockout mice. The time course of TNF-induced c-Jun revealed biphasic patterns of short-term (3 h) and long-term (24 h) induction. The time courses of Ser63- and Ser73-phospho c-Jun coincided with changes in total c-Jun. Among MAPK cascades, SAPK/JNK signaling was increased transiently in TNF-treated cells whereas p38MAPK and ERK1 and 2 were not changed. In addition, overexpression of NF-kappaB, and addition of ceramide and 8-Br-cAMP did not increase c-Jun or proliferation. Antisense oligonucleotides for c-Jun blocked cell proliferation induced by TNF. In conclusion, the above results demonstrate that TNF increased c-Jun by activating SAPK/JNK signaling via TNFR1 in mouse granulosa cells and the induced c-Jun resulted in increased cell proliferation.
Follicle stages
Preovulatory
Comment
This gene was found in a mouse DNA array analysis of transcripts expressed in mouse preovulatory follicles.