The DIX Domain Protein Coiled-coil-DIX1 Inhibits c-Jun N-terminal Kinase Activation by Axin and Dishevelled through Distinct Mechanisms

Wong, Chung Kai; Luo, Wen; Ying, Deng; Zou, Hai-Ying; Ye, Zhiyun; Lin, Sheng-Cai

doi:10.1074/jbc.m404598200

Cited by 40 publications

(35 citation statements)

References 31 publications

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“…As mentioned previously, Axin formed homodimer via its DIX domain (23). We found recently that Axin actually did not utilize its DIX domain to interact with Ccd1; rather, a region N-terminal to the DIX domain is critical for Axin-Ccd1 interaction (15). Whereas it was shown that the DIX domain of Axin is sufficient for complex formation with Dvl, the region of amino acid (aa) residues 530 -712 of Axin, N-terminal to the DIX domain, was also important for its direct interaction with Dvl (6).…”

mentioning

confidence: 88%

“…Plasmid Construction-Plasmids pCMV5-HA-Axin, pCMV5-Myc-Axin, pCMV5-HA-AxinC1, pCMV5-HA-AxinC2, pCMV5-Myc-Dvl2, and pCMV5-Myc-Ccd1 were constructed as described elsewhere (15,18,26). To construct pCMV5-HA/Myc-Axin DIX, mouse Axin cDNA was digested with EcoRI, blunted with Klenow fragment, and digested with BamHI.…”

Section: Methodsmentioning

confidence: 99%

“…In response to Wnt signals, Dvl forms a heterodimer with Axin through their DIX domains, leading to enhanced association of glycogen synthase kinase-3␤ with Frat and decreased phosphorylation of ␤-catenin (6,12,13). In addition, Axin interacts with a recently identified DIX domain protein, Ccd1, which is a positive Wnt regulator (14,15). Axin association with Dvl also appears to play a role in the regulation of microtubule dynamics in a ␤-catenin-independent manner (16).…”

mentioning

confidence: 99%

“…First of all, the particular deletion of the MEKK1 binding site (Axin⌬MID) failed to activate JNK, but other deletions around this region can activate JNK perfectly well (18,19). Second, Wnt pathway factors including glycogen synthase kinase-3␤, CKI, and Ccd1, can compete against MEKK1 binding, despite the fact that they bind to Axin domains far apart from their respective binding regions (15,20). Third, MEKK1 and MEKK4, which bind to Axin through distinct domains, also compete against each other for Axin binding (19).…”

mentioning

confidence: 99%

“…Dvl⌬DEP (a mutant Dvl that loses the ability to activate JNK) heterodimerization with Axin via their DIX domains abolishes JNK activation by Axin (17). The DIX domain of Ccd1 binds to an Axin domain, albeit not to the DIX domain of Axin, and inhibits MEKK binding to Axin and JNK activation (15). These protein-protein interactions must elicit conformational changes to modulate distinctive functions in controlling different signaling pathways.…”

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confidence: 99%

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Axin Contains Three Separable Domains That Confer Intramolecular, Homodimeric, and Heterodimeric Interactions Involved in Distinct Functions

Luo

Zou

Jin

et al. 2005

Journal of Biological Chemistry

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mentioning

confidence: 88%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Axin Contains Three Separable Domains That Confer Intramolecular, Homodimeric, and Heterodimeric Interactions Involved in Distinct Functions

Luo

Zou

Jin

et al. 2005

Journal of Biological Chemistry

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The MEK kinases MEKK4/Ssk2p facilitate complexity in the stress signaling responses of diverse systems

Bettinger

Amberg

2007

J of Cellular Biochemistry

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The mammalian JNK/p38 MAP kinase kinase kinase MEKK4 and the Saccharomyces cerevisiae Ssk2p are highly homologous. MEKK4 can replace all of the known functions of Ssk2p in yeast, including functioning in the high osmolarity glycerol (HOG) MAPK pathway and the recently described actin recovery pathway. MEKK4 and Ssk2p share a number of conserved domains and appear to be activated by a similar mechanism. Binding of an activating protein to the N-terminal region alleviates auto-inhibition and causes the kinase to auto-phosphorylate, resulting in activation. In this review we will examine the role of the MAP kinase kinase kinase isoform Ssk2p/MEKK4 in the adaptation of both yeast and mammalian systems to specific external stimuli. Recent work has provided a wealth of information about the activation, regulation, and functions of these MEKK kinases to extra-cellular signals. We will also highlight evidence supporting a role for MEKK4 in mediating actin recovery following osmotic shock in mammalian cells.

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DIXDC1 increases the invasion and migration ability of non‐small‐cell lung cancer cells via the PI3K‐AKT/AP‐1 pathway

Liu

Fan

et al. 2013

Molecular Carcinogenesis

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DIX domain containing 1 (DIXDC1), is a human homolog of Ccd1, a recently identified DIX domain containing protein in zebrafish. DIXDC1 protein was detected in human colorectal adenocarcinoma tissues and was found to be correlated with a high cell proliferation index. We demonstrated DIXDC1 overexpression in 55% (92/167) of non-small cell lung cancer (NSCLC) cases, compared to adjacent noncancerous lung tissues (P < 0.01). Overexpression of DIXDC1 was associated with lymph node metastasis and more advanced TNM stage (P < 0.001 and P = 0.001, respectively). Kaplan-Meier survival curves and log-rank testing indicated that overexpression of DIXDC1 correlated with worse overall survival in NSCLC (P = 0.031). DIXDC1 was more abundant in seven NSCLC lines than the bronchial cell line HBE, and modulation of its expression regulated AP-1 activity; MMP2, MMP7, and MMP9 protein and mRNA; and invasion ability. Metalloproteinase induction was reversed by PI3K/AKT and AP-1 inhibition. These results suggest DIXDC1 is associated with stage and prognosis in NSCLC, and may promote invasion and migration through PI3K-AKT/AP-1-dependent activation of metalloproteinases.

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The DIX Domain Protein Coiled-coil-DIX1 Inhibits c-Jun N-terminal Kinase Activation by Axin and Dishevelled through Distinct Mechanisms

Cited by 40 publications

References 31 publications

Axin Contains Three Separable Domains That Confer Intramolecular, Homodimeric, and Heterodimeric Interactions Involved in Distinct Functions

Axin Contains Three Separable Domains That Confer Intramolecular, Homodimeric, and Heterodimeric Interactions Involved in Distinct Functions

The MEK kinases MEKK4/Ssk2p facilitate complexity in the stress signaling responses of diverse systems

DIXDC1 increases the invasion and migration ability of non‐small‐cell lung cancer cells via the PI3K‐AKT/AP‐1 pathway

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