Work

Regulation of the NF-κB-inducing Kinase by Tumor Necrosis Factor Receptor-associated Factor 3-induced Degradation

Year: 2004

Type: article

Abstract: The NF-kappaB family of transcription factors plays a pivotal role in regulation of diverse biological processes, including immune responses, cell growth, and apoptosis. Activation of NF-kappaB is mediated by both canonical and noncanonical signaling pathways. Although the canonical pathway has been extensively studied, the mechanism mediating the noncanonical pathway is still poorly understood. Recent studies have identified the NF-kappaB-inducing kinase (NIK) as a key component of the noncanonical pathway of NF-kappaB activation; however, how the signaling function of NIK is regulated remains unknown. We report here that one important mechanism of NIK regulation is through its dynamic interaction with the tumor necrosis factor receptor-associated factor 3 (TRAF3). TRAF3 physically associates with NIK via a specific sequence motif located in the N-terminal region of NIK; this molecular interaction appears to target NIK for degradation by the proteasome. Interestingly, induction of noncanonical NF-kappaB signaling by extracellular signals involves degradation of TRAF3 and the concomitant enhancement of NIK expression. These results suggest that induction of noncanonical NF-kappaB signaling may involve the rescue of NIK from TRAF3-mediated negative regulation.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m403286200

Authors: Gongxian Liao, Minying Zhang, Edward W. Harhaj, Shao-Cong Sun

Institutions: Pennsylvania State University, Harvard University

Language: English

Topic: NF-κB Signaling Pathways

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430