We previously reported that RNF148 was involved in the ubiquitination-mediated degradation of CHAC2. However, its molecular mechanism was not determined. In this study, we investigated the role and mechanism of RNF148 in the progression of colorectal cancer (CRC), especially in the process of ubiquitination-mediated degradation of CHAC2. Our results revealed that RNF148 was upregulated in most CRC tissues, and its expression significantly correlated with the 3-year overall survival rate and most clinicopathological parameters of CRC patients. Furthermore, RNF148 served as an independent prognostic biomarker of CRC and promoted CRC cell proliferation and migration while inhibiting cell apoptosis and sensitivity to 5-FU. Mechanistically, RNF148 used its protease-associated domain to bind to the CHAC domain of CHAC2 and target it for degradation. In addition, we identified two phosphorylation and three ubiquitination residues of CHAC2 and identified Y118 and K102 as the critical phosphorylation and ubiquitination residues, respectively. We also identified CHAC2's and RNF148's interacting proteins and discovered their potential interaction network. In conclusion, our current study unveiled the role of RNF148 in CRC and the mechanism of RNF148 in the ubiquitination-mediated degradation of CHAC2, which shed light on providing potential prognostic biomarkers and molecular targets for CRC patients.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/carcin/bgae002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Deciphering the role of the MALT1-RC3H1 axis in regulating GPX4 protein stability.
Proc Natl Acad Sci U S A
January 2025
State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
Ferroptosis, a unique form of iron-dependent cell death triggered by lipid peroxidation accumulation, holds great promise for cancer therapy. Despite the crucial role of GPX4 in regulating ferroptosis, our understanding of GPX4 protein regulation remains limited. Through FACS-based genome-wide CRISPR screening, we identified MALT1 as a regulator of GPX4 protein.
View Article and Find Full Text PDFLOC730101 improves ovarian cancer drug sensitivity by inhibiting autophagy-mediated DNA damage repair via BECN1.
Cell Death Dis
December 2024
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital and School of Basic Medical Science, Central South University, Changsha, Hunan, China.
Drug resistance and recurrence are still the bottlenecks in the clinical treatment of ovarian cancer (OC), seriously affecting patients' prognosis. Therefore, it is an urgent challenge for OC to be overcome towards precision therapy by studying the mechanism of OC drug resistance, finding new drug resistance targets and developing new effective treatment strategies. In this study, we found that lncRNA LOC730101 played an essential role in attenuating drug resistance in OC.
View Article and Find Full Text PDFGain of pancreatic beta cell-specific SCD1 improves glucose homeostasis by maintaining functional beta cell mass under metabolic stress.
Diabetologia
December 2024
Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China.
Aims/hypothesis: The key pancreatic beta cell transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA) is critical for the maintenance of mature beta cell function and phenotype. The expression levels and/or activities of MafA are reduced when beta cells are chronically exposed to diabetogenic stress, such as hyperglycaemia (i.e.
View Article and Find Full Text PDFMechanistic exploration of ubiquitination-mediated pathways in cerebral ischemic injury.
Mol Biol Rep
November 2024
Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India.
The ubiquitin-proteasome system (UPS) plays a pivotal role in regulating protein homeostasis and cellular processes, including protein degradation, trafficking, DNA repair, and cell signaling. During cerebral ischemia, ischemic conditions profoundly disrupt UPS activity, leading to proteasomal dysfunction and the accumulation of abnormal proteins. This imbalance contributes to neuronal injury and cell death observed in ischemic stroke.
View Article and Find Full Text PDFBacterial Effector Screening Reveals RNF214 as a Virus Restriction Factor in Mammals.
bioRxiv
November 2024
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Article Synopsis
- Arboviruses, transmitted by arthropods, are a significant public health threat, prompting research into host factors that inhibit their infection for prevention and treatment strategies.* -
- A study screened 210 effector proteins from bacteria in bat and human cells, identifying three effectors (IpaH4, SopB, SidM) that boost arbovirus replication and highlighting the specific roles of various effectors.* -
- The research particularly focused on IpaH4's mechanism, revealing that it targets RNF214, an antiviral protein, for degradation, suggesting that RNF214 is crucial for innate immunity against arboviruses.*
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!