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Beschreibung

Death domain-associated protein 6 (UniProt: Q9UER7, also known as Daxx, hDaxx, ETS1-associated protein 1, EAP1, Fas death domain-associated protein) is encoded by the DAXX (also known as BING2, DAP6) gene (Gene ID: 1616) in human. Daxx is a homomultimeric protein that is dispersed throughout the nucleoplasm, in PML/POD/ND10 nuclear bodies, and in nucleoli. It serves as a transcription corepressor that represses transcriptional potential of several sumoylated transcription factors. It down-regulates basal and activated transcription and its repressor activity is modulated by its recruitment to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively. It is reported to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may thereby influence TNFRSF6-dependent apoptosis. It also acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress conditions, in association with the deubiquitinating USP7, it prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53 that leads to TP53 ubiquitination and proteasomal degradation. However, upon DNA damage, its association with MDM2 and USP7 is disrupted, which results in increased MDM2 autoubiquitination and consequently, MDM2 degradation and TP53 stabilization. It also acts as targeting component of the chromatin remodeling complex ATRX:DAXX that has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats. However, it does not affect the ATPase activity of ATRX, but alleviates its transcription repression activity.