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Cited by 105Cancer-related Molecular PathwaysCell death mechanisms and regulationChromatin Remodeling and Cancer

Daxx Cooperates with the Axin/HIPK2/p53 Complex to Induce Cell Death

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Li, Qinxi, Wang, Xuan, Wu, Xiaoling, Rui, Yanning, Liu, Wei, Wang, Jifeng, Wang, Xinghao, Liou, Yih-Cherng +2 more·2007·Cancer Research
DOI 10.1158/0008-5472.can-06-1671

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Abstract

Daxx, a death domain–associated protein, has been implicated in proapoptosis, antiapoptosis, and transcriptional regulation. Many factors known to play critically important roles in controlling apoptosis and gene transcription have been shown to associate with Daxx, including the Ser/Thr protein kinase HIPK2, promyelocytic leukemia protein, histone deacetylases, and the chromatin remodeling protein ATRX. Although it is clear that Daxx may exert multiple functions, the underlying mechanisms remain far from clear. Here, we show that Axin, originally identified for its scaffolding role to control β-catenin levels in Wnt signaling, strongly associates with Daxx at endogenous levels. The Daxx/Axin complex formation is enhanced by UV irradiation. Axin tethers Daxx to the tumor suppressor p53, and cooperates with Daxx, but not DaxxΔAxin, which is unable to interact with Axin, to stimulate HIPK2-mediated Ser46 phosphorylation and transcriptional activity of p53. Interestingly, Axin and Daxx seem to selectively activate p53 target genes, with strong activation of PUMA, but not p21 or Bax. Daxx-stimulated p53 transcriptional activity was significantly diminished by small interfering RNA against Axin; Daxx fails to inhibit colony formation in Axin−/− cells. Moreover, UV-induced cell death was attenuated by the knockdown of Axin and Daxx. All these results show that Daxx cooperates with Axin to stimulate p53, and implicate a direct role for Axin, HIPK2, and p53 in the proapoptotic function of Daxx. We have hence unraveled a novel aspect of p53 activation and shed new light on the ultimate understanding of the Daxx protein, perhaps most pertinently, in relation to stress-induced cell death. [Cancer Res 2007;67(1):66–74]

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  • In glioblastomas, significant effects of miRNAs occur indirectly rather than by direct targeting.

    “These data are also consistent with findings in glioblastomas that significant effects of miRNAs occur indirectly rather than by direct targeting (24,43).”

    From MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells (2008) · cites this paper as [24]

    The Discussion passages describe Daxx, Axin, p53 and apoptosis, including experiments using siRNA against Axin. Searches for glioblastoma, miRNAs and indirect versus direct targeting found no passage in our copy addressing the attributed finding. The paper’s use of siRNA does not establish a claim about miRNA effects in glioblastomas. (LLM, conf=0.76)

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Cited by

Sorted by citations

Authors
Li, Q., Wang, X., Wu, X., Rui, Y., Liu, W., Wang, J., Wang, X., Liou, Y.-C., Ye, Z., & Lin, S.-C.
Affiliations
  • Xiamen University (CN)
  • 2Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China;
  • Hong Kong University of Science and Technology (HK)
  • National University of Singapore (SG)
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2007-01-01
Volume
67
Issue
1
Pages
66-74
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-06-1671
OpenAlex
W2159154322
Cited by
105
References
0
Citations by year
2026: 3 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 7 · 2012: 9
FWCI
4.85
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion)
Funders
  • Johns Hopkins University
  • National Natural Science Foundation of China (B06016)
  • Hong Kong University of Science and Technology
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
DAXX, Axin, HIPK2, p53, apoptosis, p53 phosphorylation, UV-induced cell death, stress-induced cell death, protein complex formation, PUMA, Wnt signaling, β-catenin, transcriptional activation
MeSH terms
Carrier Proteins, Cell Nucleus, HeLa Cells, Humans, Nuclear Proteins, Phosphorylation, Repressor Proteins, Ultraviolet Rays, Transcriptional Activation, Tumor Suppressor Protein p53, Apoptosis, Protein Serine-Threonine Kinases, Molecular Chaperones, Cytochromes c, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Co-Repressor Proteins, Axin Protein

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