tailieunhanh - Báo cáo khoa học: Tumor necrosis factor receptor cross-talk

Extensive research has been performed to unravel the mechanistic signaling pathways mediated by tumor necrosis factor receptor 1 (TNFR1), by con-trast there is limited knowledge on cellular signaling upon activation of TNFR2. | ỵFEBS Journal MINIREVIEW Tumor necrosis factor receptor cross-talk Petrus J. W. Naude Johan A. den Boer Paul G. M. Luiten and Ulrich L. M. Eisel Departments of Molecular Neurobiology and BiologicalPsychiatry University of Groningen The Netherlands Keywords apoptosis cross-talk NF-kappa B TNFR1 TNFR2 TNF receptor associated factor TRAF inhibitor of apoptosis IAP protein kinase B Akt PI3K RIP Correspondence U. L. M. Eisel Department of Molecular Neurobiology University of Groningen . Box 11103 NL-9700 CC Groningen The Netherlands Fax 31 50 363 2331 Tel 31 50 363 2366 E-mail Received 12 October 2010 revised 22 December 2010 accepted 7 January 2011 doi Extensive research has been performed to unravel the mechanistic signaling pathways mediated by tumor necrosis factor receptor 1 TNFR1 by contrast there is limited knowledge on cellular signaling upon activation of TNFR2. Recently published data have revealed that these two receptors not only function independently but also can influence each other via cross-talk between the different signaling pathways initiated by TNFR1 and TNFR2 stimulation. Furthermore the complexity of this cross-talk is also dependent on the different signaling kinetics between TNFR1 and TNFR2 by which a delicate balance between cell survival and apoptosis can be maintained. Some known signaling factors and the kinetics that are involved in the receptor cross-talk between TNFR1 and TNFR2 are the topic of this review. Introduction Tumor necrosis factor-alpha TNF-a was discovered 30 years ago as a product of immune activation. In the last three decades an impressive amount of knowledge has been obtained regarding the biological functions of TNF as well as the signaling mechanisms engaged by its receptors. TNF primarily occurs as a type II transmembrane protein of 26 kDa which can be cleaved by the metalloprotease TNF-a-converting enzyme to a 17 kDa TNF protein that is biologically active in a .