Post-translational control of NF-κB signaling by ubiquitination.
The transcription factor nuclear factor-kappa B (NF-κB) controls a number of essential cellular functions, including the immune response, cell proliferation, and apoptosis. NF-κB signaling must be engaged temporally and spatially and well orchestrated to prevent aberrant activation because loss of normal regulation of NF-κB is a major contributor to a variety of pathological diseases, including inflammatory diseases, autoimmune diseases, and cancers. Thus, understanding the molecular mechanisms controlling NF-κB activation is an important part of treatment of these relevant diseases. Although NF-κB transcriptional activity is largely regulated by nuclear translocation, post-translational modification of NF-κB signaling components, including phosphorylation, ubiquitination, acetylation, and methylation, has emerged as an important mechanism affecting activity. Many proteins have been shown to ubiquitinate and regulate NF-κB activation at the receptor signaling complex in response to a variety of ligands, such as tumor necrosis factor, interleukin-1, and Toll-like receptor ligands. In this review, we discuss our current knowledge of ubiquitination patterns and their functional role in NF-κB regulation.
Research Institute for Medical Science, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea.
Minho
M
Won
Research Institute for Medical Science, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea.
Hee Sun
HS
Byun
Research Institute for Medical Science, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea.
Kyeong Ah
KA
Park
Research Institute for Medical Science, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea. gmhur@cnu.ac.kr.|Department of Pharmacology, Research Institute for Medical Science, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea. gmhur@cnu.ac.kr.
Gang Min
GM
Hur
D000818:Animals; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D054875:Ubiquitination / Q000502:physiology*
D016328:NF-kappa B
IKK; NF-κB; Post-translational modification; Receptor signaling complex; Ubiquitination