The p53 target gene Wig-1 encodes a double-stranded-RNA-binding zinc finger protein. We show here that Wig-1 binds to p53 mRNA and stabilizes it through an AU-rich element (ARE) in the 3' UTR of the p53 mRNA. This effect is mirrored by enhanced p53 protein levels in both unstressed cells and cells exposed to p53-activating stress agents. Thus, the p53 target Wig-1 is a previously undescribed ARE-regulating protein that acts as a positive feedback regulator of p53, with implications both for the steady-state levels of p53 and for the p53 stress response. Our data reveal a previously undescribed link between the tumor suppressor p53 and posttranscriptional gene regulation via AREs in mRNA.
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http://dx.doi.org/10.1073/pnas.0900862106 | DOI Listing |
In p53-deficient cancers, targeting cholesterol metabolism has emerged as a promising therapeutic approach, given that p53 loss dysregulates sterol regulatory element-binding protein 2 (SREBP-2) pathways, thereby enhancing cholesterol biosynthesis. While cholesterol synthesis inhibitors such as statins have shown initial success, their efficacy is often compromised by the development of acquired resistance. Consequently, new strategies are being explored to disrupt cholesterol homeostasis more comprehensively by inhibiting its synthesis and intracellular transport.
View Article and Find Full Text PDFToxicol Res (Camb)
January 2025
Yunnan Provincial Key Laboratory of Public Health and Biosafety and School of Public Health, Kunming Medical University, No. 1168 Chunrongxi Road, Chenggong, Kunming, Yunnan 650500, China.
This study explores the role of Argonaute 2 (AGO2) in the induction of apoptosis by arsenic in 16HBE cells and investigates the association between AGO2 expression and arsenic exposure in a human population. By silencing AGO2 with siRNA, we examined its impact on cell viability and apoptosis using CCK-8, HO-PI, and JC-1 assays, complemented by qRT-PCR and Western blot analyses for gene and protein expressions. Our findings revealed a significant correlation between AGO2 expression and levels of exposure to inorganic arsenic (iAs), which was more pronounced than with other arsenic forms such as monomethylarsonic (MMA) and dimethylarsinic acids (DMA).
View Article and Find Full Text PDFGenes Dis
March 2025
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA.
Targeting oncogenes and their interactive partners is an effective approach to developing novel targeted therapies for cancer and other chronic diseases. We and others have long suggested the MDM2 oncogene being an excellent target for cancer therapy, based on its p53-dependent and -independent oncogenic activities in a variety of cancers. The MYC family proteins are transcription factors that also regulate diverse biological functions.
View Article and Find Full Text PDFToxicol Res
January 2025
Department of Pharmacology, College of Medicine, Chungnam National University, 266, Munhwa-ro, Jung-gu, Daejeon, 35015 Republic of Korea.
Over the last decade, the functions of PHD finger protein 20 (PHF20) in several signaling processes have been studied, including those of protein kinase B (PKB)-mediated phosphorylation, p53 regulation, muscle differentiation, and histone modification including histone H3 lysine 4 (H3K4) methylation. One PHF20 human mutation lacks the first nonspecific lethal complex of the component that binds to H3K4me2 to facilitate cancer cell survival. In carcinoma cells, PHF20 expression is regulated by PKB; PHF20 becomes phosphorylated when DNA is damaged, thus inhibiting the p53 activity that maintains cancer cell survival.
View Article and Find Full Text PDFCell Rep
January 2025
Translational Cardiomyology Laboratory, Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Histology and Medical Embryology Unit, Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy. Electronic address:
Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, arises in skeletal muscle and remains in an undifferentiated state due to transcriptional and post-transcriptional regulators. Among its subtypes, fusion-negative RMS (FN-RMS) accounts for the majority of diagnoses in the pediatric population. MicroRNAs (miRNAs) are non-coding RNAs that modulate cell identity via post-transcriptional regulation of messenger RNAs (mRNAs).
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