Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TNF-receptor-associated factors (TRAFs) are intracellular proteins that bind to the cytoplasmic portion of TNF receptors and mediate downstream signaling. The six known TRAF proteins play overlapping yet distinct roles in controlling immune responses as well as cellular processes such as activation of NF-kappaB and JNK signaling pathways. For example, CD40 binds to TRAF2, TRAF3 and TRAF6 to control B cell differentiation, proliferation and growth. In contrast, binding of lymphotoxin-beta receptor (LTbetaR) to TRAF2 and TRAF5 propagates signals leading to activation of NF-kappaB, while binding to TRAF3 induces negative regulation of this pathway and leads to apoptosis in tumor cells. Binding recognition is mediated by specific contacts of a consensus recognition sequence in the partner with residues in a hydrophobic crevice on the TRAF molecule. Since each of these protein-protein interactions occurs within this same binding crevice, it appears that TRAF-mediated cellular mechanisms may be regulated, in part, by the level of expression or recruitment of the adaptor proteins or receptors that are competing for the crevice. The specific contacts of CD40, LTbetaR and BAFF-R have been defined in crystal structures of the complex with TRAF3. In addition, the downstream regulator TANK and the viral oncogenic protein LMP1 from the Epstein Barr virus also bind to the same TRAF crevice and these contacts have also been described crystallographically. Comparison of these five crystal structures has revealed that the recognition motifs in each of these proteins are accommodated in one TRAF3 binding crevice and that the binding interface is structurally and functionally adaptive. In this chapter, the molecular details of the interactions will be described and correlated with the functional implications for multiple TRAF3 roles in cellular regulation.
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PMID:Protein-protein interactions in TRAF3. 1763 21

The incidence of non-Hodgkin's lymphoma (NHL) has been increasing annually and has become a serious threat to human health. However, the pathogenesis of NHL remains unclear. The present study aimed to investigate the effect of soluble CD40 ligand (sCD40L) on NHL cells and its underlying mechanism. Cell Counting kit-8 assay and flow cytometry apoptosis experiments were conducted to investigate the effects of sCD40L on cell proliferation and apoptosis. Western blotting was performed to detect the protein expression levels of BAX, Bcl-2, ERK, p-ERK, JNK, p-JNK, p38, p-p38 and c-JUN. The results of the present study demonstrated that exogenous sCD40L significantly inhibited the proliferation and promoted the apoptosis of Raji and CA46 cells. Additionally, exogenous sCD40L promoted the apoptosis of lymphoma cells by activating the JNK signaling pathway.
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PMID:Soluble CD40 ligand inhibits the growth of non-Hodgkin's lymphoma cells through the JNK signaling pathway. 3328 67