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MKK4 activates non-canonical NFκB signaling by promoting NFκB2-p100 processing

Title
MKK4 activates non-canonical NFκB signaling by promoting NFκB2-p100 processing
Authors
Kim J.S.Kim E.J.Kim H.-S.Kurie J.M.Ahn Y.-H.
Ewha Authors
김희선안영호
SCOPUS Author ID
김희선scopus; 안영호scopus
Issue Date
2017
Journal Title
Biochemical and Biophysical Research Communications
ISSN
0006-291XJCR Link
Citation
vol. 491, no. 2, pp. 337 - 342
Keywords
c-Jun N-Terminal kinase (JNK)Mitogen-activated protein kinase kinase-4 (MKK4)NFκB non-canonical pathwaySenescence
Publisher
Elsevier B.V.
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The NFκB family of transcription factors is crucial for innate or adaptive immunity, inflammation, and diseases including cancer. The two NFκB signaling pathways (canonical and non-canonical) differ from each other in extracellular signals, membrane receptors, signaling adaptors, and dimer subunits. The p52 (NFκB2) subunit, which participates in the non-canonical pathway, is generated by ubiquitin-mediated processing of the p100 precursor. Here, we found that NFκB2 processing and activation were mediated by mitogen-activated protein kinase kinase-4 (MKK4) and its substrate c-Jun N-terminal kinase (JNK). In MKK4-null mouse embryonic fibroblasts (MEFs), serum- and lymphotoxin β receptor (LTβR) antibody-induced processing of p100 and nuclear translocation of p52 were found to be defective. Serum and LTβR antibody activated the MKK4-JNK signaling pathway, and SP600125, a JNK inhibitor, blocked p100 processing. Cellular senescence, one of the responses regulated by the non-canonical NFκB pathway, was observed more frequently in MKK4-null MEFs than in wildtype cells. These results suggest that the MKK4/JNK-dependent pathway regulates NFκB2 processing/activation and, through this mechanism, MKK4 and NFκB2 control cellular growth and senescence. © 2017 Elsevier Inc.
DOI
10.1016/j.bbrc.2017.07.099
Appears in Collections:
의과대학 > 의학과 > Journal papers
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