Lung carcinoma (H1299) cells deficient in p53 (p53(-/-)) express large amounts of urokinase-type plasminogen activator (uPA) protein and uPA mRNA, and exhibit slower degradation of uPA mRNA than that of p53-expressing nonmalignant Beas2B human airway epithelial cells. Expression of p53 protein in H1299 cells, upon transfection with p53 cDNA, suppressed basal as well as uPA-induced expression of uPA protein in both conditioned media and cell lysates, and decreased the level of steady-state uPA mRNA primarily due to increased uPA mRNA turnover. Inhibition of p53 expression by RNA silencing (SiRNA) in Beas2B cells enhanced basal and uPA-mediated uPA protein and mRNA expression with stabilization of uPA mRNA. Purified p53 binds to the uPA mRNA 3' untranslated region (UTR) in a sequence-specific manner and endogenous uPA mRNA associates with p53 protein isolated from Beas2B cytosolic extracts. p53 binds to a 35-nucleotide uPA 3'UTR sequence and insertion of this sequence into beta-globin mRNA accelerates degradation of otherwise stable beta-globin mRNA. These observations confirm a new role for p53 as a uPA mRNA binding protein that down-regulates uPA mRNA stability and decreases cellular uPA expression.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542451 | PMC |
| http://dx.doi.org/10.1165/rcmb.2007-0406OC | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Hippocampal Viral-Mediated Urokinase Plasminogen Activator (uPA) Overexpression Mitigates Stress-Induced Anxiety and Depression in Rats by Increasing Brain-Derived Neurotrophic Factor (BDNF) Levels.
Biomolecules
December 2024
Division of Biochemistry, University of Fribourg, 1700 Fribourg, Switzerland.
Emerging evidence suggests the serine protease, urokinase plasminogen activator (uPA), may play an important role in the modulation of mood and cognitive functions. Also, preliminary evidence indicates that uPA modulates BDNF activity that is known to be involved in the pathogenesis of mood disorders. However, the physiological functions of uPA in specific brain regions for mediating stress-related emotional behaviors remain to be elucidated.
View Article and Find Full Text PDFCold Inducible RNA-Binding Protein Promotes the Development of Alzheimer's Disease Partly by Inhibition of uPA in Astrocytes.
Degener Neurol Neuromuscul Dis
December 2024
Department of Neurosurgery, First Medical Center of the Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
Background: Cold inducible RNA-binding protein (CIRP) is an important danger-associated molecular pattern involved in tissue-specific and systemic inflammation related to inflammation and Alzheimer's disease (AD). However, the precise roles and mechanism of CIRP in the functional changes in astrocytes during the development of AD are still unknown. This study aimed to assess gene expression alterations in astrocytes after they overexpress CIRP (oe-CIRP) and to explore the relationship between abnormal CIRP expression and AD.
View Article and Find Full Text PDFA new insight on alleviating the inhibitory effect of aflatoxin B1 on muscle development in grass carp (): The effect of 4-Methylesculetin in vivo and in vitro.
Anim Nutr
December 2024
Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China.
Aflatoxin B1 (AFB1), an important fungal toxin, exists mainly in plant feed ingredients and animals consuming feed contaminated with AFB1 will have reduced growth and impaired health condition mainly due to oxidative stress and reduced immunity. Our previous study found that AFB1 caused oxidative damage and inhibited muscle development of zebrafish. 4-Methylesculetin (4-ME), a coumarin derivative, is now used in biochemistry and medicine widely because of its antioxidant function.
View Article and Find Full Text PDFPotential Nephroprotective Effect of uPA against Ischemia/Reperfusion-Induced Acute Kidney Injury in αMUPA Mice and HEK-293 Cells.
Biomedicines
October 2024
Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
The incidence of acute kidney injury (AKI) has been steadily increasing. Despite its high prevalence, there is no pathogenetically rational therapy for AKI. This deficiency stems from the poor understanding of the pathogenesis of AKI.
View Article and Find Full Text PDFPravastatin Protects Cytotrophoblasts from Hyperglycemia-Induced Preeclampsia Phenotype.
Cells
September 2024
Artemis Biotechnologies LLC, Temple, TX 76504, USA.
Unlabelled: There are no effective therapies to prevent preeclampsia (PE). Pravastatin shows promise by attenuating processes associated with PE such as decreased cytotrophoblast (CTB) migration, aberrant angiogenesis, and increased oxidative stress. This study assesses the effects of pravastatin on hyperglycemia-induced CTB dysfunction.
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!