Scientists from institutions such as the Anschutz School of Medicine at the University of Colorado have discovered and characterized a specific protein that is primarily involved in the specific mechanisms that inhibit the progression of different types of tumors.
Understanding how cancer occurs is crucial for designing effective personalized cancer therapies. For many years, researchers have known that cancer begins with mutations in certain types of genes, one of which is called “tumor suppressors”, Tumor suppressor genes block uncontrolled cell proliferation in malignant cells and initiate a cell elimination process called apoptosis (a form of cell death). Mutations in tumor suppressor genes can cause these genes to lose function, ultimately promoting the occurrence of cancer.
Recently, in a research report titled “FAM193A is a positive regulator of p53 activity” published in the international journal Cell Reports, scientists from institutions such as the Anschutz School of Medicine at the University of Colorado discovered a special protein and described its characteristics. The protein is mainly involved in the special mechanisms that inhibit the progression of different types of tumors. This tumor suppressor gene, called TP53, can effectively limit the occurrence and growth of many different tumor types throughout the human body, and it is also the most frequently mutated tumor suppressor gene in human cancer. This gene encodes a protein called p53, which is also a powerful inhibitor of cell proliferation and an inducing protein for cell apoptosis.
Researcher Professor Zdenek Andrysik stated that in over half of the cancer cases, TP53 does not undergo mutations but remains dormant. Therefore, many efforts have been made to develop new drugs to reactivate this latent form of p53 for cancer treatment. However, most cancers respond to the activation of p53, and these drugs temporarily block cell proliferation. A better response to these drugs is to eliminate cancer cells through cell apoptosis. Therefore, it is particularly important for researchers to understand which factors are necessary for effective p53-targeted cancer therapy.
In order to solve this knowledge gap, researcher Maria Szwarc et al. used a multidisciplinary experimental method (including genetic screening using CRISPR technology) to destroy all genes in the human genome one by one, and can accurately clarify which genes are required for full activation of p53. Researchers have identified a special protein called FAM193A through screening, which scientists know little about. FAM193A is a powerful and widespread positive regulator of p53 activity. Subsequent research results indicate that FAM193A is necessary for stabilizing the p53 protein and its function.
The relevant research results indicate that FAM193A can intervene in cytokines that typically inhibit p53 function (i.e. MDM2 and MDM4 proteins), which are often overactive in cancer; Researchers have found that FAM193A can counteract the MDM4 protein, thereby releasing p53 to block the proliferation and survival of cancer cells; Consistent with these research findings, researchers also found that high levels of FAM193A in certain tumor types may be associated with better prognosis in cancer patients; When researchers discovered in genetic screening that FAM193A might serve as a partner for p53, there was very little information about FAM193A.
However, after conducting advanced computational analysis on a large-scale database spanning hundreds of cancer cell types and human tumors, researchers discovered a functional connection between p53 and FAM193A. These findings may be one step closer to developing effective p53-based anticancer therapies that may need to consider the FAM193A protein, Future researchers will focus on finding new methods to enhance the activity of these companion factors that effectively inhibit tumors. In summary, the results of this study identified that FAM193A protein may serve as an important positive regulator of p53.
Reference
Maria M. Szwarc，Anna L. Guarnieri，Molishree Joshi, et al. FAM193A is a positive regulator of p53 activity, Cell Reports (2023). DOI:10.1016/j.celrep.2023.112230