Cullin 4B (CUL4B) is a member of the Cullin RING E3 ligase family, which is found to be overexpressed in multiple cancers, thus facilitating tumorigenesis and progression. However, the correlation between CUL4B and p53 in colorectal cancer cells (CRC) remains to be further elucidated. In this study, we newly identified that CUL4B functions as a negative regulator of p53, thereby facilitating CRC tumorigenesis and progression. Our data has demonstrated that CUL4B was frequently overexpressed in CRC tissues, and its upregulation was closely correlated with disease progression and poor prognosis. Moreover, CUL4B knockdown suppressed cell proliferation, invasion and epithelial-mesenchymal transition (EMT) of CRC cells. Mechanistically, CUL4B depletion increased the expression of p53 protein and its downstream targets p21, PUMA and MDM2. Furthermore, CUL4B depletion prolonged the half-life of p53 protein, and CUL4B is a binding partner of MDM2. In conclusion, our study shed new lights on the complex regulatory network between CUL4B and p53, and clarifies this CUL4B-p53 axis contributes greatly to CRC tumorigenesis and progression.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.prp.2021.153520 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
RHEB neddylation by the UBE2F-SAG axis enhances mTORC1 activity and aggravates liver tumorigenesis.
EMBO J
January 2025
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China.
Small GTPase RHEB is a well-known mTORC1 activator, whereas neddylation modifies cullins and non-cullin substrates to regulate their activity, subcellular localization and stability. Whether and how RHEB is subjected to neddylation modification remains unknown. Here, we report that RHEB is a substrate of NEDD8-conjugating E2 enzyme UBE2F.
View Article and Find Full Text PDFCell free supernatants of Bifidobacterium adolescentis and Bifidobacterium longum suppress the tumor growth in colorectal cancer organoid model.
Sci Rep
January 2025
Department of Surgery, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
The probiotic gut microbiome and its metabolites are pivotal in regulating host metabolism, inflammation, and immunity. Host genetics, colonization at birth, the host lifestyle, and exposure to diseases and drugs determine microbial composition. Dysbiosis and disruption of homeostasis in the beneficial microbiome have been reported to be involved in the tumorigenesis and progression of colorectal cancer (CRC).
View Article and Find Full Text PDFCREB3L1 facilitates pancreatic tumor progression and reprograms intratumoral tumor-associated macrophages to shape an immunotherapy-resistance microenvironment.
J Immunother Cancer
January 2025
State Key Laboratory of Systems Medicine for Cancer of Oncology Department and Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Background: To date, a growing body of evidence suggests that unfolded protein response (UPR) sensors play a vital role in carcinogenesis. However, it remains unclear whether they are involved in pancreatic ductal adenocarcinoma (PDAC) and how they relate to clinical outcomes. This study aims to investigate the biological function and mechanism of how a novel UPR sensor, CREB3L1 works in PDAC and further evaluate its clinical application prospect.
View Article and Find Full Text PDFALKBH5 facilitates tumor progression via an m6A-YTHDC1-dependent mechanism in glioma.
Cancer Lett
January 2025
Department of Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282 China. Electronic address:
N-methyladenosine (m6A) methylation, is a well-known epigenetic modification involved in various biological processes, including tumorigenesis. However, the role of AlkB homolog 5 (ALKBH5), a critical component of m6A modification, remains unclear in glioma. This study investigates the function of ALKBH5 in glioma progression and its potential as a therapeutic target.
View Article and Find Full Text PDFHigh Tumoral KPNA2 Expression Is a PotentialBiomarker for Poor Prognosis in Advanced Neuroblastoma Patients.
Cancer Diagn Progn
January 2025
Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan.
Background/aim: Karyopherin alpha 2 (KPNA2) has been reported to be associated with cancer aggressiveness and treatment resistance via transporting several cargo proteins into the nucleus, such as cancer-promoting E2F and DNA repair-related MRN complex. Recent studies have highlighted the KPNA2 functions in tumorigenesis and the progression of various cancers. However, the importance of KPNA2 expression has yet to be elucidated in clinical neuroblastoma patients.
View Article and Find Full Text PDFWant 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!