Ask about this productRelated genes to: RAD18 antibody
- Gene:
- RAD18 NIH gene
- Name:
- RAD18 E3 ubiquitin protein ligase
- Previous symbol:
- -
- Synonyms:
- RNF73
- Chromosome:
- 3p25.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-07-01
- Date modifiied:
- 2019-01-21
Related products to: RAD18 antibody
Related articles to: RAD18 antibody
- By promoting replication through DNA lesions, translesion synthesis (TLS) DNA polymerases protect against chromosomal instability and tumorigenesis. However, it is not known whether TLS in mammalian cells operates in conjunction with the replisome or in postreplicational gaps and how that impacts genomic stability. Here we show that TLS in human cells operates in close coordination with the replisome and that ATR stabilizes the replisome at the stalled replication fork (RF). In ATR-inhibited cells, the CMG helicase and DNA synthesis components of the replisome disassemble from RFs stalled at DNA lesions, and the composition of TLS and DNA synthesis components and the ensuing TLS and replication mechanisms at the stalled RFs are altered drastically from those in ATR-proficient cells. These alterations include the lack of requirement for Rad18-dependent PCNA ubiquitination for TLS by Polη and primer synthesis by the newly identified PrimPol--PolA1/PolA2 Polα complex. These results reveal the coupling of TLS to DNA replication, thus providing a means for protection against chromosome instability. - Source: PubMed
Publication date: 2026/05/15
Yoon Jung-HoonSellamuthu KarthiJohnson Robert EPrakash LouisePrakash Satya - RAD18, a key E3 ubiquitin ligase implicated in DNA repair and genome stability, is tightly linked to cancer malignant progression, yet its pan-cancer prognostic and immunotherapeutic value remains poorly defined. Herein, we performed a comprehensive pan-cancer multi-omics analysis and validated the oncogenic mechanisms of RAD18 in liver hepatocellular carcinoma, pancreatic adenocarcinoma and triple-negative breast cancer via in vitro and in vivo assays. RAD18 was significantly overexpressed in 22 cancer types, associated with gene mutation, hypomethylation, poor prognosis and favorable diagnostic efficacy, serving as an independent poor prognostic factor for multiple cancers. Mechanistically, RAD18 promoted tumor proliferation, migration and immunosuppressive microenvironment remodeling by activating the AKT/mTOR/c-Myc axis and regulating TGF-β1/PD-L1 expression. Moreover, low RAD18 expression predicted a favorable response to immune checkpoint blockade therapy, while its high expression correlated with anti-PD-1 resistance in triple-negative breast cancer. Collectively, our findings identify RAD18 as a potential pan-cancer prognostic biomarker and immunotherapeutic target, with targeting RAD18 holding promise for reversing immunotherapy resistance in solid tumors. - Source: PubMed
Publication date: 2026/05/11
Zhu JinfengHuang QianLiang QingchunYi Wenjun - The hepatitis B virus (HBV) X protein (HBx) is a key player in viral transcription, replication, and HBV-associated hepatocarcinogenesis. Several novel HBx-interacting host cellular factors: DDX1, DDX3, MOV10 RNA helicases, INI1/hSNF5 chromatin-remodeling factor, Rad18 DNA repair enzyme, and CPSF6 cleavage factor were identified. DDX1, DDX3, and MOV10 colocalized with HBx in cytoplasmic foci or aggregates. In contrast, INI1/hSNF5 and CPSF6 relocalized with HBx in nuclear speckles, interchromatin granule clusters (IGCs), and/or PML-nuclear bodies. Rad18 sequestered HBx in the nucleoli. Importantly, DDX3, MOV10, and INI1/hSNF5 restricted HBV replication, whereas CPSF6 facilitated HBV replication. Furthermore, DDX1 enhanced HBx-mediated NF-κB transcription, whereas MOV10 and Rad18 inhibited it. Altogether, HBx-interacting host factors determine dynamic nuclear and cytoplasmic localization of HBx and regulate HBV replication and HBx-mediated transcription. - Source: PubMed
Publication date: 2026/05/02
Ariumi Yasuo - Protein ubiquitination regulates diverse cellular processes, and its dysregulation contributes to human disease, including cancer. E2 ubiquitin‑conjugating enzymes share a conserved UBC fold in which surface loops fine‑tune catalysis and partner interactions, yet the roles of individual loops remain incompletely defined. Here, we identify loop 3-a component of the "backside" β2-β3 hairpin-as a conserved structural and allosteric element in Rad6‑family E2s. Structural and bioinformatic analyses of yeast Rad6 and its human homologs (UBE2A/UBE2B) reveal that loop 3 forms an overlapping triple β‑turns, with variable first turn and a highly conserved second/third turn that links catalytic regulation to E3 ligase engagement. Systematic mutagenesis of the yeast Rad6 backside β‑turn (residues 42-51) shows that this element is required in vivo for Bre1‑dependent histone H2B Lys123 monoubiquitination, Rad18‑dependent PCNA monoubiquitination, and Ubr1/Ubr2‑dependent polyubiquitination and degradation of Sml1 and N‑end rule substrates, and related biological processes. Charge‑reversal mutations at backside β‑turn Glu49 and Asp50 disrupt E3 binding, whereas cancer‑relevant substitutions in kink‑inducing prolines (Pro43/Pro47) impair mono‑ and polyubiquitination without abolishing E3 interactions. Certain backside β‑turn mutations, including cancer-relevant variants, compromise steady-state levels following DNA damage, revealing them as conditional null or loss-of-function alleles. NMR spectroscopy demonstrates that Pro43/Pro47 mutations induce long‑range structural perturbations from backside β‑turn into the front‑face catalytic pocket, correlating with reduced in vitro ubiquitination activity. Deletion or alanine replacement of the β‑turn destabilizes yeast Rad6 and human UBE2A/UBE2B. Together, these findings establish the loop 3/backside β‑turn as a critical structural element of Rad6‑family enzymes. - Source: PubMed
Publication date: 2026/05/07
Chandrasekharan Mahesh BShukla Prakash KLeng Andrew MChen Hui-HsuanGanguly RajarshiNewell Nicholas - Aim: Validate the association RAD18 Arg302Gln (rs373572) and OGG1 Ser326Cys (rs1052133) - with Renal Cell Carcinoma (RCC) susceptibility and histopathological characterization. - Source: PubMed
Altemimi Iftikhar Khdhair AbbasAmeen Binan Adil MohammedAl-Terehi Mona NHussein Liwaa Mahdi