Although early studies have suggested that the oncoprotein Mdm2 is the primary E3 ubiquitin ligase for the p53 tumor suppressor, an increasing amount of data suggests that p53 ubiquitination and degradation are more complex than once thought. The discoveries of MdmX, HAUSP, ARF, COP1, Pirh2, and ARF-BP1 continue to uncover the multiple facets of this pathway. There is no question that Mdm2 plays a pivotal role in downregulating p53 activities in numerous cellular settings. Nevertheless, growing evidence challenges the conventional view that Mdm2 is essential for p53 turnover.
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http://dx.doi.org/10.1016/j.molcel.2006.01.020 | DOI Listing |
Biochim Biophys Acta Mol Cell Res
January 2025
Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector-V, Salt Lake, Kolkata- 700091 & 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India. Electronic address:
The MDM2/MDMX-p53 circuitry is essential for controlling the development, apoptosis, immune response, angiogenesis, senescence, cell cycle progression, and proliferation of cancer cells. Research has demonstrated that USP7 exerts strong control over p53, MDM2, and MDMX stability, with multiple mediator proteins influencing the USP7-p53-MDM2/MDMX axis to modify p53 expression level and function. In cases where p53 is of the wild type (Wt-p53) in tumors, inhibiting USP7 promotes the degradation of MDM2/MDMX, leading to the activation of p53 signaling.
View Article and Find Full Text PDFCell Death Differ
January 2025
Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry/Hubei Province of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Aging is a major risk factor for Alzheimer's disease (AD). With the prevalence of AD increased, a mechanistic linkage between aging and the pathogenesis of AD needs to be further addressed. Here, we report that a small ubiquitin-related modifier (SUMO) modification of p53 is implicated in the process which remarkably increased in AD patient's brain.
View Article and Find Full Text PDFCell Rep
January 2025
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA; The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:
Mutation or deletion of the deubiquitinase USP7 causes Hao-Fountain syndrome (HAFOUS), which is characterized by speech delay, intellectual disability, and aggressive behavior and highlights important unknown roles of USP7 in the nervous system. Here, we conditionally delete USP7 in glutamatergic neurons in the mouse forebrain, triggering disease-relevant phenotypes, including sensorimotor deficits, impaired cognition, and aggressive behavior. Although USP7 deletion induces p53-dependent neuronal apoptosis, most behavioral abnormalities in USP7 conditional knockout mice persist following p53 loss.
View Article and Find Full Text PDFActa Pharmacol Sin
January 2025
Department of Pharmacology, National Key Laboratory of Frigid Zone Cardiovascular Diseases, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, 150086, China.
Eukaryotic translation initiation factor 4A1 (eIF4A1) is an ATP-dependent RNA helicase that participates in a variety of biological and pathological processes such as cell proliferation and apoptosis, and cancer. In this study we investigated the role of eIF4A1 in ischemic heart disease. The myocardial ischemia/reperfusion (I/R) model was established in mice by ligation of the left anterior descending artery for 45 min with the subsequent reperfusion for 24 h; cultured neonatal mouse ventricular cardiomyocytes (NMVCs) treated with HO (200 μM) or H/R (12 h hypoxia and 12 h reoxygenation) were used for in vitro study.
View Article and Find Full Text PDFOncol Lett
March 2025
Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
Chemoresistance is a major obstacle in the treatment of gastric cancer (GC). Notably, aberrant expression of microRNAs (miRs) is closely related to tumor development and progression. In the present study, the role of miR-424-5p in the chemoresistance of GC was investigated.
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