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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
- 김희선; 안영호
- SCOPUS Author ID
- 김희선; 안영호
- Issue Date
- 2017
- Journal Title
- Biochemical and Biophysical Research Communications
- ISSN
- 0006-291X
- Citation
- Biochemical and Biophysical Research Communications vol. 491, no. 2, pp. 337 - 342
- Keywords
- c-Jun N-Terminal kinase (JNK); Mitogen-activated protein kinase kinase-4 (MKK4); NFκB non-canonical pathway; Senescence
- Publisher
- Elsevier B.V.
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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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