TY - JOUR
T1 - An F-box protein, FBXW5, negatively regulates TAK1 MAP3K in the IL-1β signaling pathway
AU - Minoda, Yasumasa
AU - Sakurai, Hiroaki
AU - Kobayashi, Takashi
AU - Yoshimura, Akihiko
AU - Takaesu, Giichi
N1 - Funding Information:
We thank T. Yoshioka, M. Ohtsu, and E. Fujimoto for technical assistance; and Y. Nishi for preparing the manuscript. The pcDNA3-TAP vector was kindly provided by Drs. M. Matsumoto and K.I. Nakayama. This work was supported by special grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO, 07-4); the Naito Foundation; the Takeda Science Foundation; and the Princess Takamatsu Cancer Research Fund (07-23912).
PY - 2009/4/10
Y1 - 2009/4/10
N2 - TAK1, a member of the MAP3K family, plays an essential role in activation of JNK/p38 MAPKs and IKK in the IL-1β and TNFα signaling pathway. Upon stimulation, TAK1 is rapidly and transiently activated. While the activation mechanism of TAK1 in these signaling pathways is well characterized, how its activity is terminated still remains unclear. To identify the molecule(s) involved in TAK1 regulation, we performed tandem affinity purification (TAP) in HeLa cells stably expressing TAP-tagged TAK1. FBXW5, an F-box family protein, was identified as a previously unknown component of the IL-1β-induced TAK1 complex. FBXW5 associated with endogenous TAK1 in an IL-1β-dependent manner. Overexpression of FBXW5 inhibited IL-1β-induced activation of JNK/p38 MAPKs and NF-κB as well as phosphorylation of TAK1 on Thr187. Conversely, knockdown of FBXW5 resulted in the prolonged activation of TAK1 upon IL-1β stimulation. These results suggest that FBXW5 negatively regulates TAK1 in the IL-1β signaling pathway.
AB - TAK1, a member of the MAP3K family, plays an essential role in activation of JNK/p38 MAPKs and IKK in the IL-1β and TNFα signaling pathway. Upon stimulation, TAK1 is rapidly and transiently activated. While the activation mechanism of TAK1 in these signaling pathways is well characterized, how its activity is terminated still remains unclear. To identify the molecule(s) involved in TAK1 regulation, we performed tandem affinity purification (TAP) in HeLa cells stably expressing TAP-tagged TAK1. FBXW5, an F-box family protein, was identified as a previously unknown component of the IL-1β-induced TAK1 complex. FBXW5 associated with endogenous TAK1 in an IL-1β-dependent manner. Overexpression of FBXW5 inhibited IL-1β-induced activation of JNK/p38 MAPKs and NF-κB as well as phosphorylation of TAK1 on Thr187. Conversely, knockdown of FBXW5 resulted in the prolonged activation of TAK1 upon IL-1β stimulation. These results suggest that FBXW5 negatively regulates TAK1 in the IL-1β signaling pathway.
KW - F-box protein
KW - Interleukin-1β (IL-1β)
KW - MAP3K
KW - Proteasome
KW - TAK1
KW - Tandem affinity purification (TAP)
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U2 - 10.1016/j.bbrc.2009.02.052
DO - 10.1016/j.bbrc.2009.02.052
M3 - Article
C2 - 19232515
AN - SCOPUS:62049085542
SN - 0006-291X
VL - 381
SP - 412
EP - 417
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -