5kdm

Structural highlights

Function

[MTP_EBVA8] Tegument protein that plays a role in the inhibition of host intrinsic defenses to promote viral early gene activation. Interacts with host DAXX and thereby disrupts the complex between DAXX and ATRX. Suppresses the DAXX-ATRX dependent deposition of histone H3.3 on viral chromatin allowing viral transcription. May also play a role in virus entry at attachment or membrane fusion steps.[UniProtKB:P03179] [DAXX_HUMAN] Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress condition, in association with the deubiquitinating USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and subsequent proteasomal degradation. Upon DNA damage, its association with MDM2 and USP7 is disrupted, resulting in increased MDM2 autoubiquitination and consequently, MDM2 degradation, which leads to TP53 stabilization. Proposed to mediate activation of the JNK pathway and apoptosis via MAP3K5 in response to signaling from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis. In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated apoptosis may not involve DAXX. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Down-regulates basal and activated transcription. Seems to act as a transcriptional corepressor and inhibits PAX3 and ETS1 through direct protein-protein interaction. Modulates PAX5 activity. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively.^{[1] [2] [3] [4]}

References

1. ↑ Hollenbach AD, McPherson CJ, Mientjes EJ, Iyengar R, Grosveld G. Daxx and histone deacetylase II associate with chromatin through an interaction with core histones and the chromatin-associated protein Dek. J Cell Sci. 2002 Aug 15;115(Pt 16):3319-30. PMID:12140263
2. ↑ Zhao LY, Liu J, Sidhu GS, Niu Y, Liu Y, Wang R, Liao D. Negative regulation of p53 functions by Daxx and the involvement of MDM2. J Biol Chem. 2004 Nov 26;279(48):50566-79. Epub 2004 Sep 10. PMID:15364927 doi:10.1074/jbc.M406743200
3. ↑ Lin DY, Huang YS, Jeng JC, Kuo HY, Chang CC, Chao TT, Ho CC, Chen YC, Lin TP, Fang HI, Hung CC, Suen CS, Hwang MJ, Chang KS, Maul GG, Shih HM. Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors. Mol Cell. 2006 Nov 3;24(3):341-54. PMID:17081986 doi:10.1016/j.molcel.2006.10.019
4. ↑ Tang J, Qu LK, Zhang J, Wang W, Michaelson JS, Degenhardt YY, El-Deiry WS, Yang X. Critical role for Daxx in regulating Mdm2. Nat Cell Biol. 2006 Aug;8(8):855-62. Epub 2006 Jul 16. PMID:16845383 doi:10.1038/ncb1442