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Role of the ASK1-SEK1-JNK1-HIPK1 Signal in Daxx Trafficking and ASK1 Oligomerization

Authors
 Jae J. Song  ;  Yong J. Lee 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.278(47) : 47245-47252, 2003 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2003
MeSH
Active Transport, Cell Nucleus ; Adaptor Proteins, Signal Transducing ; Carrier Proteins/metabolism* ; Cell Line, Tumor ; Dimerization ; Glucose/deficiency ; Humans ; Intracellular Signaling Peptides and Proteins* ; MAP Kinase Kinase 4* ; MAP Kinase Kinase Kinase 5 ; MAP Kinase Kinase Kinases/metabolism* ; MAP Kinase Signaling System* ; Mitogen-Activated Protein Kinase 8 ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; Nuclear Proteins/metabolism* ; Phosphorylation ; Protein Kinases/metabolism* ; Protein Transport
Keywords
12968034
Abstract
Overexpression of JNK binding domain inhibited glucose deprivation-induced JNK1 activation, relocalization of Daxx from the nucleus to the cytoplasm, and apoptosis signal-regulating kinase 1 (ASK1) oligomerization in human prostate adenocarcinoma DU-145 cells. However, SB203580, a p38 inhibitor, did not prevent relocalization of Daxx and oligomerization of ASK1 during glucose deprivation. Studies from in vivo labeling and immune complex kinase assay demonstrated that phosphorylation of Daxx occurred during glucose deprivation, and its phosphorylation was mediated through the ASK1-SEK1-JNK1-HIPK1 signal transduction pathway. Data from immunofluorescence staining and protein interaction assay suggest that phosphorylated Daxx may be translocated to the cytoplasm, bind to ASK1, and subsequently lead to ASK1 oligomerization. Mutation of Daxx Ser667 to Ala results in suppression of Daxx relocalization during glucose deprivation, suggesting that Ser667 residue plays an important role in the relocalization of Daxx. Unlike wild-type Daxx, a Daxx deletion mutant (amino acids 501–625) mainly localized to the cytoplasm, where it associated with ASK1, activated JNK1, and induced ASK1 oligomerization without glucose deprivation. Taken together, these results show that glucose deprivation activates the ASK1-SEK1-JNK1-HIPK1 pathway, and the activated HIPK1 is probably involved in the relocalization of Daxx from the nucleus to the cytoplasm. The relocalized Daxx may play an important role in glucose deprivation-induced ASK1 oligomerization.
Files in This Item:
T200307037.pdf Download
DOI
10.1074/jbc.M213201200
Appears in Collections:
5. Research Institutes (연구소) > Institute for Cancer Research (암연구소) > 1. Journal Papers
Yonsei Authors
Song, Jae Jin(송재진) ORCID logo https://orcid.org/0000-0001-8183-9550
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/114627
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