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Title: Daxx cooperates with the axin/HIPK2/p53 complex to induce cell death
Authors: Li, Q.
Wang, X.
Wu, X.
Rui, Y.
Liu, W.
Wang, J.
Wang, X.
Liou, Y.-C. 
Ye, Z.
Lin, S.-C.
Issue Date: 1-Jan-2007
Citation: Li, Q., Wang, X., Wu, X., Rui, Y., Liu, W., Wang, J., Wang, X., Liou, Y.-C., Ye, Z., Lin, S.-C. (2007-01-01). Daxx cooperates with the axin/HIPK2/p53 complex to induce cell death. Cancer Research 67 (1) : 66-74. ScholarBank@NUS Repository.
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 ATBX. 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 BNA 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. ©2007 American Association for Cancer Research.
Source Title: Cancer Research
ISSN: 00085472
DOI: 10.1158/0008-5472.CAN-06-1671
Appears in Collections:Staff Publications

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