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ncover how USP7 protects the tumor suppressor protein p53 by inhibiting Mdm2, becoming a key player in the fight against cancer
At the forefront of cancer research, USP7 (ubiquitin-specific processing enzyme 7) has demonstrated its unique role. This enzyme was found to regulate the tumor suppressor protein p53 and fight the formation of cancer cells through its interaction with Mdm2. p53 is an important tumor suppressor protein in the human body, responsible for repairing damaged DNA and playing a key role in the cell cycle. When cells are under attack or stress, p53 can initiate a cell death program to prevent the development of cancer.
USP7, also known as HAUSP, is a deubiquitinase that cleaves deubiquitin from its substrate. This function is critical for maintaining the stability of p53, as Mdm2 is the E3 ubiquitin ligase responsible for p53 ubiquitination and degradation. Under normal circumstances, p53 levels remain low due to the action of Mdm2. However, when subjected to oncogenic stress, USP7 deubiquitinates p53, thereby protecting p53 from Mdm2-mediated degradation, which makes it play an important role in tumor suppression.
HAUSP activity significantly increases the stability of p53, suggesting that it may act as a tumor suppressor, especially when cells experience stress.
In addition, the involvement of USP7 is not limited to p53, it also plays a role in other pathways, such as its effect on chromosomal modifications. USP7 can deubiquitinate histone H2B, thereby promoting functions related to gene silencing. It interacts with the metabolic enzyme GMP synthase, and this complex can enhance its deubiquitination activity. This ingenious mechanism not only demonstrates the process of gene silencing in Drosophila, but also appears to be critical in human cells.
Research on drug addiction has also shown the potential of USP7. USP7 cooperates with the scaffold protein Maged1 to mediate monoubiquitination of histone H2A in the brain, a modification that is significantly increased after chronic cocaine use, which may contribute to the development of cocaine-adaptive behaviors. The link between genetic variants and drug addiction further confirms the importance of USP7 in brain responses and opens new directions for future therapies.
In chronic cocaine use, the regulatory role of USP7 significantly affects behavioral adaptation and provides a potential target for the treatment of cocaine use disorder.
Even more exciting is the association of USP7 with certain human cancers. It was first discovered while studying herpes simplex virus (HSV), and its interaction with the EBNA1 protein in Epstein-Barr virus (EBV) was later discovered. EBNA1 can competitively bind to USP7 with p53, thereby inhibiting the stabilization of p53, which shows how the virus regulates the tumor suppressor pathway of cells. This discovery highlights the potential application of USP7 in anti-cancer therapy.
With the deepening of research, scientists gradually realized that the function of USP7 is not only to maintain the stability of p53. It also plays an important role in many cellular processes, such as its effect on PTEN in different breast cancer types and its variation in neurodevelopmental disorders. These findings suggest that USP7 may become a therapeutic target that may lead to new treatments for cancer and neurological diseases in the future.
Reflecting on this series of research results, we cannot help but ask: How will USP7 be used more effectively in the development of anti-cancer therapies in the future to bring greater benefits to human health?
