Recognition of TRAIP with TRAFs: Current understanding and associated diseases

Abstract

TNF receptor proteins were primarily recognized as adaptor proteins that ligate with the tumor necrosis factor receptor (TNFR)-associated factor (TNFR) family to execute various signaling pathways. However, recent studies showed that they act as a signal-transducing molecules and are reported to have a functional role as a Toll/interleukin-1 receptor family member. Seven members of this family have been identified to date. Among TNF receptor family, TRAF7 does not share a common TRAF domain homology. The tumor necrosis factor receptor associated factor (TRAF) domain comprises of about 230 amino acid motif at the C-terminal region that has the capability to bind TNFR and execute different downstream signaling pathways. Moreover, N-terminal RING and ZINC finger constituted by the tumor necrosis factor associated protein 2 and tumor necrosis factor associated protein 6 are critical and execute various downstream signaling events. TRAF proteins have emerged as critical regulators that provide the cellular response to stress and lead to cell death. Nuclear factor kappa beta (NF-KB) and c-Jun N-terminal kinases (JNK) pathways are activated through tumor necrosis factor associated protein 2, tumor necrosis factor associated protein 5 and tumor necrosis factor associated protein 6 members. TRAF proteins in pathogenesis were observed from their abnormal expression in diseased tissue and in normal tissue, suggesting its important role in physiological processes. Recently, unique specificity of TRAF4 for glycoprotein Ibβ (GPIbβ) and glycoprotein VI (GPVI) in human platelets has been reported. The multifunctional effects of TRAIP (TNF) interacting protein in many cellular signaling pathways emerged as very important signaling molecule. Furthermore, the new insights into the structure of TRAF members along with new studies involved in health and disease prompted to explore their role particularly the TNF receptor associated proteins with novel inhibitor protein TRAIP (TNF) interacting protein and human diseases associated with it. As such, this review emphasis on tumor necrosis factor receptor associated proteins, present their current understanding with novel inhibitor protein TRAIP (TNF) interacting protein.

Keywords: Apoptosis; Nuclear factor kappa beta; TNF receptor; TNF receptor proteins; TRAIP (TNF) interacting protein.