p202, an interferon (IFN) inducible protein, is a phosphonuclear protein involved in the regulation of cell cycle, apoptosis, and differentiation. E2F1 belongs to the E2F family of proteins that are important cell cycle regulators in promoting cell growth. On the other hand, the deregulated expression of E2F1 also triggers apoptosis independent of p53 status. It has been well documented that p202 is able to inhibit cell growth by binding to E2F1 and abolishing the E2F1-mediated transcriptional activation of S-phase genes. However, it is not known whether E2F1-mediated apoptosis can be counteracted by p202 expression. Here, we show that E2F1-mediated apoptosis induced by the infection of an E2F1-expressing adenoviral vector (Ad-E2F1) was greatly diminished in p202-expressing prostate cancer cells. The E2F1-mediated caspase-3 activation was also reduced in p202-expressing cells infected with Ad-E2F1. Since caspase-3 is one of the E2F1 transcriptional targets, this result is consistent with the ability of p202 to inhibit the transcriptional activity of E2F1. Therefore, our results suggest a possible link between the IFN and E2F pathways in regulating apoptosis.
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http://dx.doi.org/10.1016/s0006-291x(03)00320-6 | DOI Listing |
J Cell Mol Med
May 2024
Shanghai Collaborative Innovation Center of Endoscopy, Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Colorectal cancer (CRC) is a highly prevalent malignancy affecting the digestive system on a global scale. This study aimed to explore the previously unexplored role of CHPF in the progression of CRC. Our results revealed a significant upregulation of CHPF expression in CRC tumour tissues compared to normal tissues, with its levels correlating with tumour malignancy.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2023
Section of Hematology/Oncology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
We have previously identified TopBP1 (topoisomerase IIβ-binding protein 1) as a promising target for cancer therapy, given its role in the convergence of Rb, PI(3)K/Akt, and p53 pathways. Based on this, we conducted a large-scale molecular docking screening to identify a small-molecule inhibitor that specifically targets the BRCT7/8 domains of TopBP1, which we have named 5D4. Our studies show that 5D4 inhibits TopBP1 interactions with E2F1, mutant p53, and Cancerous Inhibitor of Protein Phosphatase 2A.
View Article and Find Full Text PDFExp Ther Med
August 2023
Department of Pharmacy, The First Affiliated Hospital of HaiNan Medical University, Haikou, Hainan 570102, P.R. China.
Acute myeloid leukemia (AML) is a malignant disease that is mainly arisen from myeloid stem/progenitor cells. The pathogenesis of AML is complex. Ras-related protein member RAS oncogene GTPases (RAB) 34 protein has been reported to serve an important role in the development of cancer.
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February 2023
Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, which is a severer threaten to human health because of its extremely high morbidity and mortality. In this study, the role of Notchless homolog 1 (NLE1) in the development of NSCLC was investigated and the underlying mechanism was explored. The outcomes showed that NLE1 expression is significantly higher in tumor tissues than normal tissues, and is correlated with the pathological stage.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2023
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35222.
Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFRi) are approved for treating EGFR-mutant lung adenocarcinoma (LUAD), emergence of acquired resistance limits their clinical benefits. Several mechanisms for acquired resistance to EGFRi in LUAD have been identified; however, the molecular basis for this resistance remains unknown in ~30% of LUAD. Chromatin and DNA modifiers and their regulators play important roles in determining response to anticancer therapies.
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