Polo-like kinase 3 (Plk3) is an important mediator of the cellular responses to genotoxic stresses. In this study, we examined the physiologic function of Plk3 by generating Plk3-deficient mice. Plk3(-/-) mice displayed an increase in weight and developed tumors in various organs at advanced age. Many tumors in Plk3(-/-) mice were large in size, exhibiting enhanced angiogenesis. Plk3(-/-) mouse embryonic fibroblasts were hypersensitive to the induction of hypoxia-inducible factor-1 alpha (HIF-1 alpha) under hypoxic conditions or by nickel and cobalt ion treatments. Ectopic expression of the Plk3-kinase domain (Plk3-KD), but not its Polo-box domain or a Plk3-KD mutant, suppressed the nuclear accumulation of HIF-1 alpha induced by nickel or cobalt ions. Moreover, hypoxia-induced HIF-1 alpha expression was tightly associated with a significant down-regulation of Plk3 expression in HeLa cells. Given the importance of HIF-1 alpha in mediating the activation of the "survival machinery" in cancer cells, these studies strongly suggest that enhanced tumorigenesis in Plk3-null mice is at least partially mediated by a deregulated HIF-1 pathway.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725591PMC
http://dx.doi.org/10.1158/0008-5472.CAN-07-6182DOI Listing

Publication Analysis

Top Keywords

hif-1 alpha
16
polo-like kinase
8
hypoxia-inducible factor-1
8
factor-1 alpha
8
alpha hypoxic
8
hypoxic conditions
8
plk3-/- mice
8
nickel cobalt
8
domain plk3-kd
8
alpha
6

Similar Publications

Oxygen controls most metazoan metabolism, yet in mammals, tissue O levels vary widely. While extensive research has explored cellular responses to hypoxia, understanding how cells respond to physiologically high O levels remains uncertain. To address this problem, we investigated respiratory epithelia as their contact with air exposes them to some of the highest O levels in the body.

View Article and Find Full Text PDF

Bacopa monnieri Extract Diminish Hypoxia-Induced Anxiety by Regulating HIF-1α Signaling and Enhancing the Antioxidant Defense System in Hippocampus.

Neuromolecular Med

January 2025

Biochemistry and Molecular Biology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221 005, India.

Hypoxia is a significant stressor, and stabilized hypoxia-inducible factor-1α (HIF-1α) regulates the expression of numerous genes, leading to various biochemical, molecular, physiological and genomic changes. The body's oxygen-sensing system activates gene expression to protect brain tissues from hypoxia. Gamma-aminobutyric acid, an inhibitory neurotransmitter, regulates brain excitability during hypoxia through the activation of HIF-1 α.

View Article and Find Full Text PDF

Diabetic nephropathy (DN) affects about one-third of patients with diabetes and can lead to end-stage renal disease despite numerous trials aimed at improving diabetic management. Non-coding RNAs (ncRNAs) represent a new frontier in DN research, as increasing evidence suggests their involvement in the occurrence and progression of DN. A growing body of evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in DN signaling pathways might serve as novel biomarkers or therapeutic targets, although this remains to be fully explored.

View Article and Find Full Text PDF

Red and blue LED light increases the survival rate of random skin flaps in rats after MRSA infection.

Lasers Med Sci

January 2025

Department of Plastic and Reconstructive Surgery, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, Anhui Province, 230601, P.R. China.

Skin flap transplantation is a conventional wound repair method in plastic and reconstructive surgery, but infection and ischemia are common complications. Photobiomodulation (PBM) therapy has shown promise for various medical problems, including wound repair processes, due to its capability to accelerate angiogenesis and relieve inflammation. This study investigated the effect of red and blue light on the survival of random skin flaps in methicillin-resistant Staphylococcus aureus (MRSA)-infected Sprague Dawley (SD) rats.

View Article and Find Full Text PDF

Objective: To explore the mechanism of hyperbaric oxygen therapy in inhibiting subchondral bone angiogenesis and delaying the progression of osteoarthritis through the PHD2/HIF-1α signaling pathway.

Methods: Mice were randomly divided into three groups (control group, osteoarthritis group, and hyperbaric oxygen treatment group). The effect of hyperbaric oxygen therapy on osteoarthritis was evaluated using Micro-CT, Safranin O-Fast Green staining, and detection of osteoarthritis inflammation markers (MMP-13, ADAMTS-5, Col2a1, and Aggrecan).

View Article and Find Full Text PDF

Want 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!