Home Death domain associated protein (Daxx), a multi-functional protein
Article
Licensed
Unlicensed Requires Authentication

Death domain associated protein (Daxx), a multi-functional protein

  • Shuang-Yang Tang , Yan-Ping Wan EMAIL logo and Yi-Mou Wu
Published/Copyright: March 5, 2016
Become an author with De Gruyter Brill
Author Information
Cellular and Molecular Biology Letters
From the journal Cellular and Molecular Biology Letters Volume 20 Issue 5

Abstract

Death domain associated protein (Daxx), a multi-functional protein, plays an important role in transcriptional regulation, cell apoptosis, carcinogenesis, anti-virus infection and so on. However, its regulatory mechanisms for both cell survival and apoptosis remain largely obscure. Our review of recent studies shows that Daxx has many interesting functional dualities and can provide a reference for further research on Daxx.

Keywords: Death domain associated protein; Function; Mutation; Expression; Localization; Interaction; Modification; Regulation; Transcription; Apoptosis

References

1. Yang, X., Khosravi-Far, R., Chang, H.Y. and Baltimore, D. Daxx, a novel Fasbinding protein that activates JNK and apoptosis. Cell 89 (1997) 1067-1076.Search in Google Scholar

2. Chang, H.Y., Nishitoh, H., Yang, X., Ichijo, H. and Baltimore, D. Activation of apoptos is signal-regulating kinase 1 (ASK 1) by the adapter protein Daxx. Science 281 (1998) 1860-63.Search in Google Scholar

3. Lindsay, C.R., Morozov, V.M. and Ishov, A.M. PML NBs (ND10) and Daxx: from nuclear structure to protein function. Front Biosci. 13 (2008) 7132-7142.Search in Google Scholar

4. Tang, M., Li, Y., Zhang, Y., Chen, Y., Huang, W., Wang, D., Zaug, A.J., Liu, D., Zhao, Y., Cech, T.R., Ma, W. and Songyang, Z. Disease mutant analysis identifies a new function of DAXX in telomerase regulation and telomere maintenance. J. Cell Sci. 128 (2015) 331-341.Search in Google Scholar

5. Kurihara, S., Hiyama, E., Onitake, Y., Yamaoka, E. and Hiyama, K. Clinical features of ATRX or DAXX mutated neuroblastoma. J. Pediatr. Surg. 49 (2014) 1835-1838.Search in Google Scholar

6. Jiao, Y., Shi, C., Edi,l BH., de-Wilde, R.F., Klimstra, D.S., Maitra, A., Schulick, R.D., Tang, L.H., Wolfgang, C.L., Choti, M.A., Velculescu, V.E., Diaz, L.A.Jr., Vogelstein, B., Kinzler, K.W., Hruban, R.H. and Papadopoulos, N. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 331 (2011) 1199-1203.Search in Google Scholar

7. Yuan, F., Shi, M., Ji, J., Shi, H., Zhou, C., Yu, Y., Liu, B., Zhu, Z. and Zhang, J. KRAS and DAXX/ATRX gene mutations are correlated with the clinicopathological features, advanced diseases, and poor prognosis in chinese patients with pancreatic neuroendocrine tumors. Int. J. Biol. Sci. 10 (2014) 957-965.Search in Google Scholar

8. de-Wilde, R.F, Heaphy, C.M, Maitra, A., Meeker, A.K., Edil, B.H., Wolfgang, C.L., Ellison, T.A., Schulick, R.D., Molenaar, I.Q., Valk, G.D., Vriens, M.R, Borel-Rinkes, I.H, Offerhaus, G.J., Hruban, R.H. and Matsukuma, K.E. Loss of ATRX or DAXX expression and concomitant acquisition of the alternative lengthening of telomeresphenotype are late events in a small subset of MEN-1 syndrome pancreatic neuroendocrine tumors. Mod. Pathol. 25 (2012) 1033-1039.Search in Google Scholar

9. Marinoni, I,, Kurrer, A.S., Vassella, E., Dettmer, M., Rudolph, T., Banz, V., Hunger, F., Pasquinelli, S., Speel, E.J. and Perren, A. Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic neuroendocrine tumors. Gastroenterology 146 (2014) 453-460.Search in Google Scholar

10. Ishov, A.M., Sotnikov, A.G., Negorev, D., Vladimirova, O.V., Neff, N., Kamitani, T., Yeh, E.T., Strauss, J.F.3rd. and Maul, G.G. PML is critical for ND10 formation and recruits the PMLinteracting protein Daxx to this nuclear structure when modified by SUMO-1. J. Cell. Biol. 147 (1999) 221-234.Search in Google Scholar

11. Yeung, P.L., Chen, L.Y., Tsai, S.C., Zhang, A. and Chen, J.D. Daxx contains two nuclear localization signals and interacts with importin alpha3. J. Cell. Biochem. 103 (2008) 456-470.Search in Google Scholar

12. Sharma, R., Sharma, A., Dwivedi, S., Zimniak, P., Awasthi, S. and Awasthi, Y.C. 4-Hydroxynonenal self-limits Fas-mediated DISC-independent apoptosis by promoting export of Daxx from nucleus to cytosol and its binding to Fas. Biochemistry 47 (2008) 143-156.Search in Google Scholar

13. Tang, S.Y., Li, L., Li, Y.L., Liu, A.Y., Yu, M.J. and Wan, Y.P. Distribution and location of Daxx in cervical epithelial cells with high risk human papillomavirus positive. Diagn. Pathol. 9 (2014) e1.10.1186/1746-1596-9-1Search in Google Scholar PubMed PubMed Central

14. Zizzi, A., Montironi, M.A., Mazzucchelli, R., Scarpelli, M., Lopez-Beltran, A., Cheng, L., Paone, N., Castellini, P. and Montironi, R. Immunohistochemical analysis of chromatin remodeler Daxx in high grade urothelial carcinoma. Diagn. Pathol. 8 (2013) e111.10.1186/1746-1596-8-111Search in Google Scholar PubMed PubMed Central

15. Tanaka, M. and Kamitani, T. Cytoplasmic relocation of Daxx induced by Ro52 and FLASH. Histochem. Cell Biol. 134 (2010) 297-306.Search in Google Scholar

16. Newhart, A., Rafalska-Metcalf, I.U., Yang, T., Negorev, D.G. and Janicki, S.M. Single-cell analysis of Daxx and ATRX-dependent transcriptional repression. J. Cell. Sci. 125 (2012) 5489-5501. Search in Google Scholar

17. Tsai, K., Chan, L., Gibeault, R., Conn, K., Dheekollu, J., Domsic, J., Marmorstein, R., Schang, L.M. and Lieberman, P.M. Viral reprogramming of the Daxx histone H3.3 chaperone during early Epstein-Barr virus infection. J. Virol. 88 (2014) 14350-14363.Search in Google Scholar

18. Tsai, K., Thikmyanova, N., Wojcechowskyj, J.A., Delecluse, H.J. and Lieberman, P.M. EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription. PLoS Pathog. 7 (2011) e1002376.10.1371/journal.ppat.1002376Search in Google Scholar PubMed PubMed Central

19. Li, L., Wen, J., Tuo, Q.H. and Liao, D.F. Effects of SUMOylation on the subcellular localization and function of DAXX. Sheng Li Xue Bao 65 (2013) 89-95.Search in Google Scholar

20. Naik, M.T., Chang, C.C., Naik, N.M., Kung, C.C., Shih, H.M. and Huang, T.H. NMR chemical shift assignments of a complex between SUMO-1 and SIM peptide derived from the C-terminus of Daxx. Biomol. NMR Assign. 5 (2011) 75-77.Search in Google Scholar

21. Sudharsan, R. and Azuma, Y. The SUMO ligase PIAS1 regulates UV-induced apoptosis by recruiting Daxx to SUMOylated foci. J. Cell Sci. 125 (2012) 5819-5829.Search in Google Scholar

22. Tang, J., Agrawal, T., Cheng, Q., Qu, L., Brewer, M.D., Chen, J. and Yang, X. Phosphorylation of Daxx by ATM contributes to DNA damage-induced p53 activation. PLoS One 8 (2013) e55813.10.1371/journal.pone.0055813Search in Google Scholar PubMed PubMed Central

23. Schreiner, S., Bürck, C., Glass, M., Groitl, P., Wimmer, P., Kinkley, S., Mund, A., Everett, R.D. and Dobner, T. Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes. Nucleic Acids Res. 41 (2013) 3532-3550.Search in Google Scholar

24. DeNizio, J.E., Elsässer, S.J. and Black, B.E. DAXX co-folds with H3.3/H4 using high local stability conferred by the H3.3 variant recognition residues. Nucleic Acids Res. 42 (2014) 4318-4331.Search in Google Scholar

25. Delbarre, E., Ivanauskiene, K., Küntziger, T. and Collas, P. DAXXdependent supply of soluble (H3.3-H4) dimers to PML bodies pending deposition into chromatin. Genome Res. 23 (2013) 440-451.Search in Google Scholar

26. Lacoste, N., Woolfe, A., Tachiwana, H., Garea, A.V., Barth, T., Cantaloube, S., Kurumizaka, H., Imhof, A. and Almouzni, G. Mislocalization of the centromeric histone variant CenH3/CENP-A in human cells depends on the chaperone DAXX. Mol. Cell. 53 (2014) 631-644.Search in Google Scholar

27. Shalginskikh, N., Poleshko, A., Skalka, A.M. and Katz, R.A. Retroviral DNA methylation and epigenetic repression are mediated by the antiviral host protein Daxx. J. Virol. 87 (2013) 2137-2150.Search in Google Scholar

28. Yao, Z., Zhang, Q., Li, X., Zhao, D., Liu, Y., Zhao, K., Liu, Y., Wang, C., Jiang, M., Li, N. and Cao, X. Death domain-associated protein 6 (Daxx) selectively represses IL-6 transcription through histone deacetylase 1 (HDAC1)-mediated histone deacetylation in macrophages. J. Biol. Chem. 289 (2014) 9372-9379. Search in Google Scholar

29. Cantrell, S.R and Bresnahan, W.A. Interaction between the human cytomegalovirus UL82 gene product(pp71)and hDaxx regulates immediateearly gene expression and viral replication. J. Virol. 79 (2005) 7792-7802.Search in Google Scholar

30. Schreiner, S. and Wodrich, H. Virion factors that target Daxx to overcome intrinsic immunity. J. Virol. 87 (2013) 10412-10422.Search in Google Scholar

31. Khaiboullina, S.F, Morzunov, S.P, Boichuk, S.V, Palotás, A., St-Jeor, S., Lombardi, V.C. and Rizvanov, A.A. Death-domain associated protein-6 (DAXX) mediated apoptosis in hantavirus infection is counter-balanced by activation of interferon-stimulated nuclear transcription factors. Virology 443 (2013) 338-348.Search in Google Scholar

32. Netsawang, J., Noisakran, S., Puttikhunt, C., Kasinrerk, W., Wongwiwat, W., Malasit, P., Yenchitsomanus, P.T. and Limjindaporn, T. Nuclear localization of dengue virus capsid protein is required for DAXX interaction and apoptosis. Virus Res. 147 (2010) 275-283.Search in Google Scholar

33. Netsawang, J., Panaampon, J., Khunchai, S., Kooptiwut, S., Nagila, A., Puttikhunt, C., Yenchitsomanus, P.T. and Limjindaporn, T. Dengue virus disrupts Daxx and NF-κB interaction to induce CD137-mediated apoptosis. Biochem. Biophys. Res. Commun. 450 (2014) 1485-1491.Search in Google Scholar

34. Gaddy, D.F. and Lyles, D.S. Oncolytic vesicular stomatitis virus induces apoptosis via signaling through PKR, Fas, and Daxx. J. Virol. 81 (2007) 2792-2804.10.1128/JVI.01760-06Search in Google Scholar PubMed PubMed Central

35. Fukuyo, Y., Kitamura, T., Inoue, M., Horikoshi, N.T., Higashikubo, R., Hunt, C.R., Usheva, A. and Horikoshi, N. Phosphorylation-dependent Lys63-linked polyubiquitination of Daxx is essential for sustained TNF-α- induced ASK1 activation. Cancer Res. 69 (2009) 7512-7517.Search in Google Scholar

36. Song, J.J. and Lee, Y.J. Role of the ASK1-SEK1-JNK1-HIPK1 signal in Daxx trafficking and ASK1 oligomerization. J. Biol. Chem. 278 (2003) 47245-47252.Search in Google Scholar

37. Yun, H.J., Yoon, J.H., Lee, J.K., Noh, K.T., Yoon, K.W., Oh, S.P., Oh, H.J., Chae, J.S., Hwang, S.G., Kim, E.H., Maul, G.G., Lim, D.S. and Choi, E.J. Daxx mediates activation-induced cell death in microglia by triggering MST1 signalling. EMBO J. 30 (2011) 2465-2476.Search in Google Scholar

38. Kwan, P.S., Lau, C.C., Chiu, Y.T., Man, C., Liu, J., Tang, K.D., Wong, Y.C. and Ling, M.T. Daxx regulates mitotic progression and prostate cancer predisposition. Carcinogenesis 34 (2013) 750-759.Search in Google Scholar

39. Kwon, T.R., Jeong, S.J., Lee, H.J., Lee, H.J., Sohn, E.J., Jung, J.H., Kim, J.H., Jung, D.B., Lu, J. and Kim, S.H. Reactive oxygen species-mediated activation of JNK and down-regulation of DAXX are critically involved in penta-O-galloyl-beta-d-glucose-induced apoptosis in chronic myeloid leukemia K562 cells. Biochem. Biophys. Res. Commun. 424 (2012) 530-537.Search in Google Scholar

40. Junn, E., Taniguchi, H., Jeong, B.S., Zhao, X., Ichijo, H. and Mouradian, M.M. Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death. Proc. Natl. Acad. Sci. USA 102 (2005) 9691-9696.Search in Google Scholar

41. Pan, W.W., Yi, F.P., Cao, L.X., Liu, X.M., Shen, Z.F., Bu, Y.Q., Xu, Y., Fan, H.Y. and Song, F.Z. DAXX silencing suppresses mouse ovarian surface epithelial cell growth by inducing senescence and DNA damage. Gene 526 (2013) 287-294.Search in Google Scholar

42. Pan, W.W., Zhou, J.J., Liu, X.M., Xu, Y., Guo, L.J., Yu, C., Shi, Q.H. and Fan, H.Y. Death domain-associated protein DAXX promotes ovarian cancer development and chemoresistance. J. Biol. Chem. 288 (2013) 13620-13630.Search in Google Scholar

43. Kumar, N., Wethkamp, N., Waters, L.C., Carr, M.D. and Klempnauer, K.H. Tumor suppressor protein Pdcd4 interacts with Daxx and modulates the stability of Daxx and the Hipk2-dependent phosphorylation of p53 at serine 46. Oncogenesis 2 (2013) e37.10.1038/oncsis.2012.37Search in Google Scholar PubMed PubMed Central

44. Zhang, H., He, J., Li, J., Tian, D., Gu, L. and Zhou, M. Methylation of RASSF1A gene promoter is regulated by p53 and Daxx. FASEB J. 27 (2013) 232-242.Search in Google Scholar

45. Giovinazzi, S., Morozov, V.M., Summers, M.K., Reinhold, W.C. and Ishov, A.M. USP7 and Daxx regulate mitosis progression and taxane sensitivity by affecting stability of Aurora-A kinase. Cell Death Differ. 20 (2013) 721-731.Search in Google Scholar

46. Li, C., Zhou, J., Wu, X., Tian, Y., Deng, J. and Liu, W. Induction of myelogenous leukemia cells with histone deacetylase inhibitors through downregulating the Daxx protein expression. J. Huazhong Univ. Sci. Technolog. Med. Sci. 29 (2009) 546-550.Search in Google Scholar

47. Lin, D.Y., Lai, M.Z., Ann, D.K. and Shih, H.M. Promyelocytic leukemia protein (PML) functions as a glucocorticoid receptor co-activator by sequestering Daxx to the PML oncogenic domains (PODs) to enhance its transactivation potential. J. Biol. Chem. 278 (2003) 15958-15965.Search in Google Scholar

48. Chang, C.C., Naik, M.T., Huang, Y.S, Jeng, J.C., Liao, P.H., Kuo, H.Y., Ho, C.C., Hsieh, Y.L., Lin, C.H., Huang, N.J., Naik, N.M., Kung, C.C., Lin, S.Y., Chen, R.H., Chang, K.S., Huang, T.H. and Shih, H.M. Structural and functional roles of Daxx SIM phosphorylation in SUMO paralogselective binding and apoptosis modulation. Mol. Cell. 42 (2011) 62-74.Search in Google Scholar

49. Xiong, G., Li, L., Sun, S., Li,T., Liao, D., Shu, C. and Tuo, Q. Subcellular localization of DAXX influence ox-LDL induced apoptosis in macrophages. Mol. Biol. Rep. 41 (2014) 7183-7190.Search in Google Scholar

50. Dionne, K.R., Zhuang, Y., Leser, J.S., Tyler, K.L. and Clarke, P. Daxx upregulation within the cytoplasm of reovirus-infected cells is mediated by interferon and contributes to apoptosis. J. Virol. 87 (2013) 3447-3460.Search in Google Scholar

51. Lee, Y.S., Dayma, Y., Park, M.Y., Kim, K.I., Yoo, S.E. and Kim, E. Daxx is a key downstream component of receptor interacting protein kinase 3 mediating retinal ischemic cell death. FEBS Lett. 587 (2013) 266-271.Search in Google Scholar

52. Hwang, S., Song, S., Hong, Y.K., Choi, G., Suh, Y.S., Han, S.Y., Lee, M., Park, S.H.,Lee, J.H., Lee, S., Bang, S.M., Jeong, Y., Chung, W.J., Lee, I.S., Jeong, G., Chung, J. and Cho, K.S. Drosophila DJ-1 decreases neural sensitivity to stress by negatively regulating Daxx-like protein through dFOXO. PLOS Genet. 9 (2013) e1003412.10.1371/journal.pgen.1003412Search in Google Scholar PubMed PubMed Central

53. Nurhayati, R.W, Ojima, Y., Nomura, N. and Taya, M. Promoted megakaryocytic differentiation of K562 cells through oxidative stress caused by near ultraviolet irradiation. Cell. Mol. Biol. Lett. 19 (2014) 590-600. Search in Google Scholar

Received: 2015-4-20
Accepted: 2015-10-19
Published Online: 2016-3-5
Published in Print: 2015-12-1

© University of Wroclaw, Poland

Articles in the same Issue

  1. How taste works: cells, receptors and gustatory perception
  2. Non-cooperative immobilization of residual water bound in lyophilized photosynthetic lamellae
  3. Coexistence of rare variant HbD Punjab [α2β2121(Glu→Gln)] and alpha 3.7 kb deletion in a young boy of Hindu family in West Bengal, India
  4. Somatic stem cell aging and malignant transformation – impact on therapeutic application
  5. 1H NMR-based metabolic profiling for evaluating poppy seed rancidity and brewing
  6. Homology arms of targeting vectors for gene insertions and CRISPR/Cas9 technology: size does not matter; quality control of targeted clones does
  7. Death domain associated protein (Daxx), a multi-functional protein
  8. In silico screening of alleged miRNAs associated with cell competition: an emerging cellular event in cancer
  9. MGL induces nuclear translocation of EndoG and AIF in caspase-independent T cell death
  10. Cerivastatin represses atherogenic gene expression through the induction of KLF2 via isoprenoid metabolic pathways
  11. Proteasomes raise the microtubule dynamics in influenza A (H1N1) virus-infected LLC-MK2 cells
  12. Purinergic signaling and the functioning of the nervous system cells
  13. The effect of cultureware surfaces on functional and structural components of differentiated 3T3-L1 preadipocytes
  14. Ramipril inhibits high glucose-stimulated up-regulation of adhesion molecules via the ERK1/2 MAPK signaling pathway in human umbilical vein endothelial cells
  15. The effect of nicotine on the expressions of the α7 nicotinic receptor gene and Bax and Bcl-2 proteins in the mammary gland epithelial-7 breast cancer cell line and its relationship to drug resistance
  16. The cloning, expression and purification of recombinant human neuritin from Escherichia coli and the partial analysis of its neurobiological activity
https://doi.org/10.1515/cmble-2015-0048
Keywords for this article
Death domain associated protein; Function; Mutation; Expression; Localization; Interaction; Modification; Regulation; Transcription; Apoptosis

Articles in the same Issue

  1. How taste works: cells, receptors and gustatory perception
  2. Non-cooperative immobilization of residual water bound in lyophilized photosynthetic lamellae
  3. Coexistence of rare variant HbD Punjab [α2β2121(Glu→Gln)] and alpha 3.7 kb deletion in a young boy of Hindu family in West Bengal, India
  4. Somatic stem cell aging and malignant transformation – impact on therapeutic application
  5. 1H NMR-based metabolic profiling for evaluating poppy seed rancidity and brewing
  6. Homology arms of targeting vectors for gene insertions and CRISPR/Cas9 technology: size does not matter; quality control of targeted clones does
  7. Death domain associated protein (Daxx), a multi-functional protein
  8. In silico screening of alleged miRNAs associated with cell competition: an emerging cellular event in cancer
  9. MGL induces nuclear translocation of EndoG and AIF in caspase-independent T cell death
  10. Cerivastatin represses atherogenic gene expression through the induction of KLF2 via isoprenoid metabolic pathways
  11. Proteasomes raise the microtubule dynamics in influenza A (H1N1) virus-infected LLC-MK2 cells
  12. Purinergic signaling and the functioning of the nervous system cells
  13. The effect of cultureware surfaces on functional and structural components of differentiated 3T3-L1 preadipocytes
  14. Ramipril inhibits high glucose-stimulated up-regulation of adhesion molecules via the ERK1/2 MAPK signaling pathway in human umbilical vein endothelial cells
  15. The effect of nicotine on the expressions of the α7 nicotinic receptor gene and Bax and Bcl-2 proteins in the mammary gland epithelial-7 breast cancer cell line and its relationship to drug resistance
  16. The cloning, expression and purification of recombinant human neuritin from Escherichia coli and the partial analysis of its neurobiological activity
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 5.11.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cmble-2015-0048/html
Scroll to top button