Checkpoints that control Myc-mediated proliferation and apoptosis are bypassed during tumorigenesis. Genes encoding polyamine biosynthetic enzymes are overexpressed in B cells from E mu-Myc transgenic mice. Here, we report that disabling one of these Myc targets, Ornithine decarboxylase (Odc), abolishes Myc-induced suppression of the Cdk inhibitors p21(Cip1) and p27(Kip1), thereby impairing Myc's proliferative, but not apoptotic, response. Moreover, lymphoma development was markedly delayed in E mu-Myc;Odc(+/-) transgenic mice and in E mu-Myc mice treated with the Odc inhibitor difluoromethylornithine (DFMO). Strikingly, tumors ultimately arising in E mu-Myc;Odc(+/-) transgenics lacked deletions of Arf, suggesting that targeting Odc forces other routes of transformation. Therefore, Odc is a critical Myc transcription target that regulates checkpoints that guard against tumorigenesis and is an effective target for cancer chemoprevention.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ccr.2005.03.036 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The role of 1-Deoxysphingolipids and Polyamines in the pathogenesis of placental syndrome.
BMC Pregnancy Childbirth
January 2025
Department of Basic Pharmaceutical Sciences, Division of Biochemistry, Recep Tayyip Erdogan University, Rize, Turkey.
Background: Placental syndrome, mainly composed of preeclampsia and fetal growth restriction, has an impact on the health of mother and baby dyads. While impaired placentation is central to their pathophysiology, the underlying molecular mechanisms remain incompletely understood. This study investigates the association between placental syndrome and metabolic alterations in 1-deoxysphingolipids (1-deoxySLs) and polyamines, along with their regulatory enzymes.
View Article and Find Full Text PDFSalivary microbiota dysbiosis and elevated polyamine levels contribute to the severity of periodontal disease.
BMC Oral Health
January 2025
Department of Life Sciences, GITAM (Deemed to be University), GITAM School of Science, Visakhapatnam, Andhra Pradesh, 530 045, India.
Background: The oral cavity is a complex environment which harbours the second largest and most diverse microflora after the gastrointestinal tract. The bacteriome in the oral cavity plays a pivotal role in promoting the health and well-being of human beings. Gingivitis, an inflammation of the gingival tissue, arises due to plaque accumulation on the teeth, often leads to periodontitis.
View Article and Find Full Text PDFIn vitro and in silico approaches manifest the anti-leishmanial activity of wild edible mushroom .
In Silico Pharmacol
December 2024
Laboratory of Cell and Molecular Biology, Department of Botany, Centre of Advanced Study, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019 India.
Visceral Leishmaniasis, caused by is the second most deadly parasitic disease, causing over 65,000 deaths annually. Synthetic drugs available in the market, to combat this disease, have numerous side effects. In this backdrop, we aim to find safer antileishmanial alternatives with minimal side effects from mushrooms, which harbour various secondary metabolites with promising efficacy.
View Article and Find Full Text PDFSupraphysiological androgen (SPA) treatment can paradoxically restrict growth of castration-resistant prostate cancer with high androgen receptor (AR) activity, which is the basis for use of Bipolar Androgen Therapy (BAT) for patients with this disease. While androgens are widely appreciated to enhance anabolic metabolism, how SPA-mediated metabolic changes alter prostate cancer progression and therapy response is unknown. Here, we report that SPA markedly increased intracellular and secreted polyamines in prostate cancer models.
View Article and Find Full Text PDFRhizophagus irregularis regulates RiCPSI and RiCARI expression to influence plant drought tolerance.
Plant Physiol
December 2024
State Key Laboratory of Conservation and Utilization of Subtropical Agro-Bioresources, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm, College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou 510642, China.
Arbuscular mycorrhizal fungi (AMF) can transfer inorganic nitrogen (N) from the soil to host plants to cope with drought stress, with arginine synthesis and NH4+ transport being pivotal processes. However, the regulatory mechanism underlying these processes remains unclear. Here, we found that drought stress upregulated expression of genes involved in the N transfer pathway and putrescine and glutathione synthesis in the mycorrhizal structures of Rhizophagus irregularis within alfalfa (Medicago sativa) roots, i.
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!