DAXX

Official Full Name

death domain associated protein

Organism

Homo sapiens

GeneID

1616

Background

This gene encodes a multifunctional protein that resides in multiple locations in the nucleus and in the cytoplasm. It interacts with a wide variety of proteins, such as apoptosis antigen Fas, centromere protein C, and transcription factor erythroblastosis virus E26 oncogene homolog 1. In the nucleus, the encoded protein functions as a potent transcription repressor that binds to sumoylated transcription factors. Its repression can be relieved by the sequestration of this protein into promyelocytic leukemia nuclear bodies or nucleoli. This protein also associates with centromeres in G2 phase. In the cytoplasm, the encoded protein may function to regulate apoptosis. The subcellular localization and function of this protein are modulated by post-translational modifications, including sumoylation, phosphorylation and polyubiquitination. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

Synonyms

DAP6; EAP1; BING2; SMIM40;

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Detailed Information

Death-Domain Associated Protein, commonly known as DAXX, is a multifunctional protein that plays a significant role in various cellular processes. DAXX is notably associated with cell apoptosis, serving as an adaptor protein that interacts with death domain-containing receptors and modulates apoptotic signaling pathways. Beyond its role in cell death regulation, DAXX is involved in diverse cellular functions, including transcriptional regulation, DNA damage response, and chromatin remodeling. Its interactions with a wide array of proteins and involvement in multiple cellular processes highlight its importance in cellular homeostasis and its potential implications in various diseases, including cancer and neurodegenerative disorders.

DAXX and Apoptosis Regulation: Orchestrating Cell Death Pathways

Death-Domain Associated Protein (DAXX) is intricately involved in the regulation of apoptosis, a fundamental process in which cells undergo programmed self-destruction. DAXX acts as a critical mediator, interfacing with death domain-containing proteins and modulating apoptotic signaling cascades. In some contexts, DAXX functions as a pro-apoptotic factor, enhancing the activation of apoptotic pathways in response to various cellular stresses. It facilitates the assembly of protein complexes that drive apoptotic events, including caspase activation and mitochondrial pathway modulation. Moreover, DAXX also participates in anti-apoptotic processes, serving as a multifaceted regulator. Its interactions with apoptotic regulators and its ability to influence both intrinsic and extrinsic apoptotic pathways underline its significance in orchestrating the delicate balance between cell survival and programmed cell death.

DAXX and Transcriptional Regulation: Mastering Genetic Expression

Death-Domain Associated Protein (DAXX) plays a pivotal role in transcriptional regulation, acting as a multifaceted modulator of genetic expression. DAXX participates in diverse cellular processes, including gene silencing, chromatin remodeling, and epigenetic modifications. It functions as a transcriptional co-repressor by associating with histone deacetylases (HDACs) and other chromatin-modifying enzymes, leading to the suppression of specific gene expression. Additionally, DAXX interacts with various transcription factors and co-regulators, influencing the activation or repression of target genes. Moreover, DAXX is involved in DNA damage response, where it modulates the expression of genes related to cell cycle regulation and DNA repair. Its intricate involvement in transcriptional control mechanisms highlights its significance in shaping cellular phenotypes and responses to various stimuli.

DAXX and DNA Damage Response: Guardians of Genomic Stability

Death-Domain Associated Protein (DAXX) plays a crucial role in the DNA damage response, a complex cellular mechanism designed to maintain genomic stability and integrity. DAXX participates in various aspects of this response, including DNA repair, cell cycle regulation, and apoptosis. It interacts with key DNA damage repair proteins, such as ATM (ataxia-telangiectasia mutated) and ATR (ATM- and Rad3-related), facilitating the activation of DNA repair pathways. Additionally, DAXX modulates the expression of genes involved in DNA damage repair, promoting efficient repair of damaged DNA strands. Furthermore, DAXX is involved in apoptosis induction following severe DNA damage, ensuring the elimination of cells with irreparable DNA lesions. Its intricate involvement in the DNA damage response highlights its significance as a guardian of genomic stability, preventing the accumulation of mutations and the development of diseases such as cancer. Understanding the role of DAXX in DNA damage response provides essential insights into the mechanisms underlying cellular protection against genomic insults.

References:

Muromoto, Ryuta. Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan vol. 132,9 (2012): 979-84. doi:10.1248/yakushi.132.979
Ishikura, Shuhei et al. "Death domain-associated protein DAXX regulates noncoding RNA transcription at the centromere through the transcription regulator ZFAT." The Journal of biological chemistry vol. 298,11 (2022): 102528. doi:10.1016/j.jbc.2022.102528

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