日本專家在新一期英國《自然—細胞生物學》雜誌上發表論文說，他們發現了促使核轉錄因子NF—κB活躍的機制。這種核轉錄因子過度活躍可導致特應性皮炎、癌症等疾病，這項成果有望成為開發相關新藥的線索。
NF—κB核轉錄因子通常在細胞漿中與某些抑制蛋白結合，呈無活性狀態。日本大阪大學的生物化學教授巖井一宏等研究人員，以人體中分解無用蛋白的泛素為研究對象，通過小鼠細胞實驗發現幾個泛素分子連接而成的聚泛素與另一種蛋白相結合，可以使NF—κB核轉錄因子開始活躍起來。
目前用於抑制NF—κB核轉錄因子活性的藥物有類固醇製劑等，但是這類藥物同時也作用於其他蛋白，由此會引發多種副作用。而巖井一宏等人的實驗顯示，聚泛素似乎只作用於NF—κB核轉錄因子。這些研究人員認為，找到抑制聚泛素作用的物質，有望為開發副作用小的相關藥物創造可能性。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Cell Biology，doi:10.1038/ncb1821，Fuminori Tokunaga，Kazuhiro Iwai
Involvement of linear polyubiquitylation of NEMO in NF-κB activation
Fuminori Tokunaga1,2,3, Shin-ichi Sakata1,2,3, Yasushi Saeki4, Yoshinori Satomi5, Takayoshi Kirisako3, Kiyoko Kamei1,3, Tomoko Nakagawa1,3, Michiko Kato3, Shigeo Murata4,6, Shoji Yamaoka7, Masahiro Yamamoto8, Shizuo Akira9, Toshifumi Takao5, Keiji Tanaka4 & Kazuhiro Iwai1,2,3
Nuclear factor-B (NF-κB) is a key transcription factor in inflammatory, anti-apoptotic and immune processes. The ubiquitin pathway is crucial in regulating the NF-κB pathway. We have found that the LUBAC ligase complex, composed of the two RING finger proteins HOIL-1L and HOIP, conjugates a head-to-tail-linked linear polyubiquitin chain to substrates. Here, we demonstrate that LUBAC activates the canonical NF-κB pathway by binding to NEMO (NF-κB essential modulator, also called IKK) and conjugates linear polyubiquitin chains onto specific Lys residues in the CC2–LZ domain of NEMO in a Ubc13-independent manner. Moreover, in HOIL-1 knockout mice and cells derived from these mice, NF-κB signalling induced by pro-inflammatory cytokines such as TNF- and IL-1 was suppressed, resulting in enhanced TNF-–induced apoptosis in hepatocytes of HOIL-1 knockout mice. These results indicate that LUBAC is involved in the physiological regulation of the canonical NF-κB activation pathway through linear polyubiquitylation of NEMO.
1 Department of Biophysics and Biochemistry, Graduate School of Medicine and Cell Biology and Metabolism Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
CREST, Japan Science Technology Corporation, Kawaguchi, Saitama 332-0012, Japan.
2 Department of Molecular Cell Biology, Graduate School of Medicine, Osaka City University, Abeno-ku, Osaka 545-8585
3 Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan.
4 Laboratory of Protein Profiling and Functional Proteomics, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
5 Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
6 Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan.
7 Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine
8 Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, 565-0871, Japan.