Ubiquitin modification possesses numerous functions, such as p53 degradation and mitochondrial translocation (39), though PIRH2 is relevant to the p53 degradation and tetramerization (40). The other two proteins (ICP0 and Ubc13) are usually not involved in p53 degradation and are related to the nucleus translocation and (41) tetramerization (42) of p53, respectively. At present, most of the studies relevant to p53 ubiquitination in larger animals have mostly focused on tumorigenesis, but a few have studied its effect around the host’s immune defense. It was reported that MeCP2 (methyl-CpG binding protein two) could promote ubiquitinationdependent p53 degradation and additional inhibit RPL5/RPL11 transcription, which at some point facilitates the carcinogenesis of breast cancer (43). Besides, RBCK1 (RANBP2-type and C3HC4-type zinc finger-containing 1) has been shown to directly interact with p53 protein and facilitate its polyubiquitination and degradation, restoring the function of p53 by RBCK1, which can be thought of a promising tactic for renal cell carcinoma therapy (44).IL-33 Protein web Additionally, the open reading frame 3 (ORF3) protein of porcine circovirus kind 2 (PCV2) could bind to PIRH2 and suppress PIRH2-mediated p53 ubiquitination, resulting in the accumulation of p53 through viral infection, and also the ORF3-induced apoptosis plays a significant role in PCV2 pathogenesis (45).TGF beta 2/TGFB2, Human So far, p53 has been poorly studied in invertebrates.PMID:24563649 It was located that p53 could regulate Mn superoxide dismutase (MnSOD) and glutathione peroxidase (GPx) to cope with acute environmental stresses in shrimp (46). Few research have shown that WSSV infection could activate the p53-dependent apoptotic pathway in shrimp (21, 22); having said that, p53 ubiquitination and its relevant mechanisms involved in the immune response against viral infection are still unknown. In our study, the mud crab was extensively made use of as an invertebrate model for the WSSV infection. The outcomes showed that the expression of HUWE1 and TRAF6 was decreased during WSSV infection, major to the interruption of p53 ubiquitination, and thus, p53 accumulated to cope with viral invasion within the mud crab. Our function could be the initially to reveal the functions and mechanisms of p53 ubiquitination inMarch 2022 Volume 96 Challenge six e02029-21 jvi.asm.orgGong et al.Journal of Virologyinvertebrates, suggesting the conservation with the p53 ubiquitination pathway in animals and its necessary roles in the antiviral immune regulation of marine invertebrates. HUWE1 and TRAF6 are E3 ligases for p53 that have been confirmed to become closely associated with tumorigenesis (18, 26). HUWE1 could serve as a important aspect linked with ARF in H1299 cells, which is crucial for both the p53-independent and p53-dependent tumor suppressor functions mediated by ARF by way of straight binding and ubiquitinating p53 (47). Apart from, TRAF6 was found to suppress mitochondrial translocation of p53 and restrict spontaneous apoptosis by mediating K63-linked ubiquitination of p53 at K24 in U2OS cells (18). In recent years, the immunological functions of HUWE1 and TRAF6 have also been studied. By way of example, the classical swine fever virus (CSFV) nonstructural protein three (NS3) is often a multifunctional protein necessary for viral replication. TRAF6 was discovered to suppress CSFV replication by way of interacting with NS3 (48). TRAF6 could protect FHM (Fathead minnow) cells from cell death induced by Singapore grouper iridovirus (SGIV) by way of repressing virus-induced production of kind I interferons (IFNs).
