The ubiquitin ligase Mdm2 targets the p53 tumor suppressor protein for proteasomal degradation. Mutating phosphorylation sites in the central domain of Mdm2 prevents p53 degradation, although it is still ubiquitylated, indicating that Mdm2 has a post-ubiquitylation function for p53 degradation. We show that Mdm2 associates with several subunits of the 19S proteasome regulatory particle in a ubi...

Loss of function mutations in the von Hippel-Lindau (pVHL) tumor suppressor protein are tumorigenic. In silico analysis of the structure and folding of WT pVHL identified in its core an aromatic tetrahedron, essential for stabilizing the protein. The mutations disrupt the aromatic tetrahedron, leading to misfolding of pVHL. Using biophysical methods we confirmed the in silico predictions, demon...

The only reported role for the conjugation of the NEDD8 ubiquitin-like molecule is control of the activity of SCF ubiquitin ligase complexes. Here, we show that the Mdm2 RING finger E3 ubiquitin ligase can also promote NEDD8 modification of the p53 tumor suppressor protein. Mdm2 is itself modified with NEDD8 with very similar characteristics to the autoubiquitination activity of Mdm2. By using ...

Nanoenzymes In article 2300191 by Wenli Diao, Hui Wei, Hongqian Guo, and co-workers, a Zr-CeO nanozyme is developed to possess enhanced activities mimicking superoxide dismutase catalase. Via scavenging intracellular reactive oxygen species, exerts remarkable effects on diminishing myeloid-derived suppressor cells M2-TAM immunosuppression simultaneously, eventually boosts anti-tumor immune resp...

Tumorigenesis, in general, is originated from two types of gene alterations, a tumor suppressor gene and a proto-oncogene/oncogene. A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from tumorigenesis. When this gene mutates, it causes a loss or reduction in its protection[1]. A proto-oncogene is a normal gene coding proteins which regulate cell growth and differentiatio...

Wild-type p53 acts as a tumor suppressor gene by protecting cells from deleterious effects of genotoxic agents through the induction of a G1/S arrest or apoptosis as a response to DNA damage. Transforming proteins of several oncogenic DNA viruses inactivate tumor suppressor activity of p53 by blocking this cellular response. To test whether hepatitis B virus displays a similar effect, we studie...

TOPORS is the first example of a protein with both ubiquitin and SUMO-1 E3 ligase activity and has been implicated as a tumor suppressor in several different malignancies. To gain insight into the cellular role of TOPORS, a proteomic screen was performed to identify candidate sumoylation substrates. The results indicate that many of the putative substrates are involved in chromatin modification...

Tumor microenvironment (TME) remodeling is one of the major research subjects in oncology. Several strategies can be implemented to modulate tumor microenvironment, particularly reprogramming myeloid cells stimulate their anti-cancer activities. Indeed, constitute component TME. Hence, it important identify molecular signatures associated cancer- promoting cells. Here, we defined phenotype and ...

TP53 is one of the most frequently-mutated and deleted tumor suppressors in cancer, with a dramatic correlation with dismal prognoses. In addition to genetic inactivation, the p53 protein can be functionally inactivated in cancer, through post-transductional modifications, changes in cellular compartmentalization, and interactions with other proteins. Here, we review the mechanisms of p53 funct...