Evolution of CG Methylation Maintenance Machinery in Plants

Cytosine methylation is an epigenetic mark present in most eukaryotic genomes that contributes to the regulation of gene expression and the maintenance of genome stability. DNA methylation mostly occurs at CG sequences, where it is initially deposited by de novo DNA methyltransferases and propagated by maintenance DNA methyltransferases (DNMT) during DNA replication. In this review, we first summarize the mechanisms maintaining CG methylation in mammals that involve the DNA Methyltransferase 1 (DNMT1) enzyme and its cofactor, UHRF1 (Ubiquitin-like with PHD and RING Finger domain 1). We then discuss the evolutionary conservation and diversification of these two core factors in the plant kingdom and speculate on potential functions of novel homologues typically observed in land plants but not in mammals.

UHRF1 Suppresses HIV-1 Transcription and Promotes HIV-1 Latency by Competing with p-TEFb for Ubiquitination-Proteasomal Degradation of Tat

HIV-1 latency is systematically modulated by host factors and viral proteins. In our work, we identified a critical role of host factor ubiquitin-like with PHD and RING finger domain 1 (UHRF1) in HIV-1 latency via the modulation of the viral protein Tat stability.

Replication of cowpox virus in macrophages is dependent on the host range factor p28/N1R

Zoonotic orthopoxvirus infections continue to represent a threat to human health. The disease caused by distinct orthopoxviruses differs in terms of symptoms and severity, which may be explained by the unique repertoire of virus factors that modulate the host’s immune response and cellular machinery. We report here on the construction of recombinant cowpox viruses (CPXV) which either lack the host range factor p28 completely or express truncated variants of p28. We show that p28 is essential for CPXV replication in macrophages of human or mouse origin and that the C-terminal RING finger domain of p28 is necessary to allow CPXV replication in macrophages.

When MARCH family proteins meet viral infections

Membrane-associated RING-CH (MARCH) ubiquitin ligases belong to a RING finger domain E3 ligases family. Recent studies have demonstrated that MARCH proteins play critical roles during various viral infections. MARCH proteins can directly antagonize different steps of the viral life cycle and promote individual viral infection. This mini-review will focus on the latest advances of MARCH family proteins' emerging roles during viral infections.

Mechanism by which TRAF6 Participates in the Immune Regulation of Autoimmune Diseases and Cancer

Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), an E3 ubiquitin ligase, is a signal transduction molecule shared by the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) family and the TNFR superfamily. TRAF6 has a unique TRAF domain and RING finger domain that mediate intracellular signaling events. In the immune system, TRAF6-mediated signaling has been shown to be critical for the development, homeostasis, and activation of a variety of immune cells, including B cells, T cells, dendritic cells, and macrophages. Although the pathogenesis and etiology of autoimmune diseases and cancer are not fully understood, it is worth noting that existing studies have shown that TRAF6 is involved in the pathogenesis and development of a variety of these diseases. Herein, we reviewed the role of TRAF6 in certain immune cells, as well as the function and potential effect of TRAF6 in autoimmune diseases and cancer. Our review indicates that TRAF6 may be a novel target for autoimmune diseases and cancer.

Blockade of TRIM59 to enhance chemosensitivity of esophageal cancer cell to cisplatin by upregulating p53 expression.

e16509 Background: TRIM59 is the one of TRIM family characterized by an N-terminal really interesting new gene (RING)-finger domain, followed by two zinc-finger domains named B2 box and a coiled-coil (CC). Ubiquitination plays a vital role in the degradation of many kinds of proteins that function in the intracellular signaling pathway, cell cycle, DNA repair and transcriptional regulation. Because of the RING-finger domain, TRIM59 protein functions as E3 ubiquitin ligase activity and can selectively target ubiquitin-modified proteins for proteasomes or degradation. In additional, accumulating finding results have shown the TRIM proteins promote positively or negatively carcinogenesis. Here we focus on the TRIM59 protein: oncogenic activity in the promoting proliferation and metastasis of esophageal cancer cell. Methods: None. Results: Human esophageal cancer cells’ motility adopts various modes resulting in the HESC progression and poor survival of patients. We proved that TRIM59 is aberrantly up-regulated in metastatic human esophageal cancer (hESC) than adjacent normal esophageal tissue, which is on behalf of poor survival and advanced TNM state among the hESC patients. At the molecular level, we proved TRIM59 as an E3 putative ubiquitin ligase targets the p53 protein leading to the increased degradation of p53 resulting in the less chemotherapy sensitivity to cisplatin. TRIM59 knockdown in hESC cell lines reduced TRIM59 expression and promotes p53 protein level and decreased the proliferation, clone formation, migration. At the same time, hESC cell lines showed more sensitive to the cisplatin in the cell line treated with knockdown of TRIM59. These findings establish the relationship between TRIM59 and p53 and chemotherapy sensitivity of cisplatin and TRIM59 may be a promising prognostic indicator for esophageal squamous cell carcinoma (ESCA) patients. Conclusions: We have confirmed that the up-regulation of TRIM59 in human esophageal cancer tissues closely correlates with poor prognosis of patients and TRIM59 serves as an oncogene promoting the proliferation and metastasis of esophageal cancer. The study demonstrates that knockdown of TRIM59 inhibited the growth and invasion of Eca109 cancer cells and strengthened the chemosensitivity to cisplatin through the mechanism of increasing the p53 expression. These results suggest that combination of TRIM59 knockdown with cisplatin might provide a promising strategy to treat the patients with esophageal cancer.

Cisplatin binds to the MDM2 RING finger domain and inhibits the ubiquitination activity

Cisplatin binds to the RING finger of MDM2, leading to the zinc-release and protein unfolding, resulting in the inhibition of MDM2-mediated ubiquitination.