RELT Human

RELT is a type I transmembrane glycoprotein characterized by a cysteine-rich extracellular domain. This domain is homologous to other TNFRSF members, such as TNFRSF19, DR3, OX40, and LTβ receptor . The messenger RNA of RELT is predominantly found in hematologic tissues, including the spleen, lymph nodes, and peripheral blood leukocytes. It is also expressed in leukemias and lymphomas .

RELT is capable of activating the NF-κB pathway, a critical transcription factor involved in immune responses. It selectively binds to tumor necrosis factor receptor-associated factor 1 (TRAF1), which is essential for signal transduction . Although the soluble form of RELT fusion protein does not inhibit the one-way mixed lymphocyte reaction, immobilized RELT can costimulate T-cell proliferation in the presence of CD3 signaling .

Emerging evidence suggests that RELT and its paralogs, RELL1 and RELL2, collectively referred to as RELTfms, are involved in various physiological processes, including cytokine signaling and pathways that promote either cell death or survival . T cells from mice lacking RELT exhibit increased responses against tumors and heightened inflammatory cytokine production . This indicates that RELT may contribute to an immunosuppressive environment for tumors .

The relationship between individual RELTfms and different cancers is complex. While some evidence suggests that RELTfms may be risk factors in certain cancers, they appear to be protective in others . Beyond cancer, RELTfms are important for processes related to microbial pathogenesis, inflammation, behavior, reproduction, and development .

RELT and its paralogs have been strongly conserved across all vertebrates, highlighting their fundamental role in vertebrate biology . This conservation underscores the importance of these proteins in maintaining immune system integrity and overall health.