The E3 ubiquitin ligase RAD18 has been identified as an oncoprotein that exhibits prometastatic properties in various types of cancer; however, the role of RAD18 in cervical cancer (CC) remains unclear. In the present study, it was revealed that increased expression of RAD18 was associated with worse prognosis of patients with CC. Knockdown of endogenous RAD18 suppressed the motility and invasiveness of CC cells, as evaluated by Transwell assays. mRNA sequencing revealed that silencing RAD18 altered the expression profile of proinflammatory mediators, such as interleukin‑1β (IL‑1β). Furthermore, exogenous IL‑1β treatment rescued RAD18‑mediated CC cell invasion. These findings indicated an underlying mechanism via which RAD18 promotes CC progression, suggesting that RAD18 may be a potential biomarker and therapeutic target for malignant CC.
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http://dx.doi.org/10.3892/mmr.2019.10564 | DOI Listing |
Cancer Med
February 2025
Centre for Medical Research, Ningbo No.2 Hospital, Ningbo, China.
Background: Hepatocellular carcinoma (HCC) is one of the most common and highly lethal cancers worldwide. RIO kinase 1 (RIOK1), a protein kinase/ATPase that plays a key role in regulating translation and ribosome assembly, is associated with a variety of malignant tumors. However, the role of RIOK1 in HCC remains largely unknown.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. Bl. 21, 1113 Sofia, Bulgaria.
Replication forks encounter various impediments, which induce fork stalling and threaten genome stability, yet the precise dynamics of fork stalling and restart at the single-cell level remain elusive. Herein, we devise a live-cell microscopy-based approach to follow hydroxyurea-induced fork stalling and subsequent restart at 30 s resolution. We measure two distinct processes during fork stalling.
View Article and Find Full Text PDFBiomolecules
January 2025
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
RAD18 is a conserved eukaryotic E3 ubiquitin ligase that promotes genome stability through multiple pathways. One of these is gap-filling DNA synthesis at active replication forks and in post-replicative DNA. RAD18 also regulates homologous recombination (HR) repair of DNA breaks; however, the current literature describing the contribution of RAD18 to HR in mammalian systems has not reached a consensus.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Biochemistry and Molecular Biology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The province and ministry co-sponsored collaborative innovation center for medical epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, 300070 Tianjin, P. R. CHINA. Electronic address:
Ubiquitination of the proliferating cell nuclear antigen (PCNA) by the budding yeast protein Rad5 have important functions in replication stress responses. Rad5 together with the Ubc13-Mms2 complex attaches Lys63-linked ubiquitin chain to a highly conserved Lys164 residue in PCNA. The reaction requires prior PCNA mono-ubiquitination by the Rad6-Rad18 complex and signals for error-free DNA damage tolerance responses.
View Article and Find Full Text PDFEmerg Microbes Infect
December 2025
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
The nuclear-cytoplasmic trafficking of matrix proteins (M) is essential for henipavirus budding, with M protein ubiquitination playing a pivotal role in this dynamic process. Despite its importance, the intricacies of the M ubiquitination cascade have remained elusive. In this study, we elucidate a novel mechanism by which Nipah virus (NiV), a highly pathogenic henipavirus, utilizes a ubiquitination complex involving the E2 ubiquitin-conjugating enzyme RAD6A and the E3 ubiquitin ligase RAD18 to ubiquitinate the virus's M protein, thereby facilitating its nuclear-cytoplasmic trafficking.
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