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A key player in cell division: How does Daxx affect the mysterious process of S phase?
With the deepening of biomedical research, the regulation of cell cycle and division has gradually received attention. In this complex process, death-associated protein 6 (Daxx) emerged with its unique function and became an important role in the cell division process. Daxx is not only involved in apoptosis, but also plays a key role in different stages of the cell cycle, especially in cell division during the S phase.
Daxx is a multifunctional protein that interacts with multiple structures in the nucleus and cytoplasm and is involved in many intranuclear processes, such as transcription and cell cycle regulation.
Early studies have shown that Daxx can interact with a variety of proteins, including the classical death receptor Fas, centriolar protein C, and transcription factor ETS1. In the nucleus, Daxx binds to other transcription factors to exert a potent transcriptional repression and regulates gene expression by interacting with transcription factors containing aggregates.
Daxx's structure and positioning
Daxx is widely expressed in various tissues of the human body, especially in the testis and thymus. At the cellular level, Daxx is present both in the cytoplasm, interacting with molecules such as the Fas receptor, and in the nucleus, interacting with intranuclear structures.
When PML-NB is missing or destroyed, Daxx is delocalized, preventing apoptosis from occurring.
Daxx co-localizes with the silencing agent ATRX during the S phase of the cell cycle, and the existence of this partnership points to the importance of Daxx in the cell cycle. The lack of Daxx expression may lead to abnormalities in the functioning of the S phase and even cause cells to form two nuclei.
The role of the cytoplasm and membranes
When the Fas receptor is stimulated, Daxx will translocate from the nucleus to the cytoplasm. Certain stress conditions, such as the breakdown of glucose, trigger the production of reactive oxygen species, which prompt Daxx to enter the cytoplasm and interact with ASK1 (apoptosis signal-regulating kinase 1).
This transport mechanism is dependent on phosphorylation, but it is unclear whether Fas receptor stimulation is mediated by ROS or CRM1.
Role in apoptosis
The role of Daxx in the process of promoting apoptosis has also attracted increasing attention. When stimulated by Fas, Daxx activates the c-JUN-N-terminal kinase (JNK) signaling pathway. This pathway is essential for regulating stress-induced cell death and also plays an important role in the development of the nervous system.
Daxx does not directly activate JNK, but activates ASK1 through the upstream JNK kinase, suggesting a positive feedback mechanism in the apoptosis process.
In addition, Daxx also exerts many other functions under the regulation of transforming growth factor β (TGF-β). Studies have shown that Daxx interacts with TGF-β type II receptor and is activated after cells are treated with TGF-β.
Daxx's multiple functions
Surprisingly, Daxx also exhibits anti-apoptotic properties. When Daxx expression is inhibited, it may lead to early lethality, and the apoptosis rate is increased in embryonic stem cells lacking the Daxx gene. The binding of Daxx to PML may confer its anti-apoptotic role.
The ubiquity of Daxx makes it play an important role in regulating transcription. Although it does not have a known DNA binding structure, it can inhibit the activity of multiple transcription factors.
In short, Daxx is not only an apoptosis-related protein, but also an indispensable participant in the regulation of the cell cycle, especially in the S phase. As research deepens, Daxx's multiple roles within cells will gradually be revealed, which makes people wonder: What new secrets will Daxx reveal in future research in cell biology?
