Search results for "cyclin-dependent kinase"
showing 10 items of 164 documents
A novel serine/threonine kinase gene, STK33 , on human chromosome 11p15.3
2001
Human chromosomal region 11p15 is known to be associated with several diseases including predispositions to develop various tumor types. In search of candidate genes, a novel human kinase gene is described, STK33, which codes for a serine/threonine protein kinase. The gene was discovered by comparative genome analysis of human chromosome 11p15.3 and its orthologous region on distal mouse chromosome 7. Human STK33 gene contains 12 exons as has been determined by the comparison to the full-length transcript amplified from human uterus RNA. Transcripts are found in a variety of tissues in at least two alternatively spliced forms as revealed by reverse transcriptase-polymerase chain reaction, c…
An increase in neural stem cells and olfactory bulb adult neurogenesis improves discrimination of highly similar odorants
2019
Adult neurogenesis is involved in cognitive performance but studies that manipulated this process to improve brain function are scarce. Here, we characterized a genetic mouse model in which neural stem cells (NSC) of the subventricular zone (SVZ) were temporarily expanded by conditional expression of the cell cycle regulators Cdk4/cyclinD1, thus increasing neurogenesis. We found that supernumerary neurons matured and integrated in the olfactory bulb similarly to physiologically generated newborn neurons displaying a correct expression of molecular markers, morphology and electrophysiological activity. Olfactory performance upon increased neurogenesis was unchanged when mice were tested on r…
Involvement of cyclin-dependent kinase-5 in the kainic acid-mediated degeneration of glutamatergic synapses in the rat hippocampus.
2011
Increased levels of glutamate causing excitotoxic damage accompany neurological disorders such as ischemia/stroke, epilepsy and some neurodegenerative diseases. Cyclin-dependent kinase-5 (Cdk5) is important for synaptic plasticity and is deregulated in neurodegenerative diseases. However, the mechanisms by which kainic acid (KA)-induced excitotoxic damage involves Cdk5 in neuronal injury are not fully understood. In this work, we have thus studied involvement of Cdk5 in the KA-mediated degeneration of glutamatergic synapses in the rat hippocampus. KA induced degeneration of mossy fiber synapses and decreased glutamate receptor (GluR)6/7 and post-synaptic density protein 95 (PSD95) levels in…
Immunohistochemical expression of Ki-67, Cyclin D1, p16INK4a, and Survivin as a predictive tool for recurrence and progression-free survival in papil…
2019
Objectives: To investigate the expression of several immunohistochemical (IHC) markers and their predictive ability for the recurrence-free and progression-free survival of papillary urothelial bladder cancer (UBC) pTa/pT1 G2 (WHO 1973) compared to classical anatomo-clinical variables using a multidimensional analysis. Materials and Methods: A population-based cohort of 213 primary stage UBC (pTa/pT1) G2 (WHO 1973) was evaluated by classic anatomopathological variables and characterized by immunohistochemistry (23 IHC markers, representative of different oncogenic pathways). The most important variables as a predictor of recurrence-free and progression-free survival were selected using mult…
Differences in DNA Methylation Patterns and Expression of the CCRK Gene in Human and Nonhuman Primate Cortices
2009
Changes in DNA methylation patterns during embryo development and differentiation processes are linked to the transcriptional plasticity of our genome. However, little is known about the evolutionary conservation of DNA methylation patterns and the evolutionary impact of epigenetic differences between closely related species. Here we compared the methylation patterns of CpG islands (CGIs) in the promoter regions of seven genes in humans and chimpanzees. We identified a block of CpGs in the cell cycle-related kinase (CCRK) gene that is more methylated in the adult human cortex than in the chimpanzee cortex and, in addition, it exhibits considerable intraspecific variation both in humans and …
The clinical significance of CDK1 expression in oral squamous cell carcinoma
2014
Objectives: To evaluate the clinical significance of cyclin-dependent kinase 1 (CDK 1 ) in 77 oral squamous cell carcinomas (OSCC) using immunohistochemical methods. Study Design: Immunohistochemical expression of CDK 1 was compared with various clinicopathological features in 77 OSCC and 60 controlled epithelia adjacent to the tumours. In addition, correlation of CDK 1 expression and prognostic and the 5-year accumulative survival rate of OSCC were investigated. Results: The CDK 1 protein was expressed in 52 cases of 77 tumor tissues (67.5%), compared with 21 cases of 60 controlled (35.0%). The expression of CDK 1 was significantly correlated with the histological grade of OSCC ( P <0.05).…
Expression of the Tumor Suppressor Gene Product p16INK4 in Benign and Malignant Melanocytic Lesions
1998
The gene MTS1 encodes p16INK4, an inhibitor of cyclin-dependent kinase 4, and is frequently deleted, mutated, or silenced by promoter methylation in melanoma cells and in the germline of familial melanoma patients. Although MTS1 may thus be the candidate melanoma suppressor gene that maps to chromosome 9p21, it is not clear how dysfunction at that locus temporally relates to melanoma progression. To further test its role in sporadic melanoma, the expression of p16INK4-protein and -mRNA was characterized in melanomas and melanocytic nevi by immunocytochemistry and in situ reverse transcriptase-polymerase chain reaction. Histologic tissue sections were immunolabeled with anti-p16INK4 antibody…
Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies
2012
Background— Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts. Methods and Results— Continuous ABI and PAD (ABI ≤0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ≈2.5 million single nucleotide polymorphisms (SNPs) in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fi…
Anti-aging activity of the Ink4/Arf locus.
2009
The proteins encoded by the Ink4/Arf locus, p16Ink4a, p19Arf and p15Ink4b are major tumour suppressors that oppose aberrant mitogenic signals. The expression levels of the locus are progressively increased during aging and genome-wide association studies have linked the locus to a number of aging-associated diseases and frailty in humans. However, direct measurement of the global impact of the Ink4/Arf locus on organismal aging and longevity was lacking. In this work, we have examined the fertility, cancer susceptibility, aging and longevity of mice genetically modified to carry one (Ink4/Arf-tg) or two (Ink4/Arf-tg/tg) intact additional copies of the locus. First, increased gene dosage of …
Deficient p27 Phosphorylation at Serine 10 Increases Macrophage Foam Cell Formation and Aggravates Atherosclerosis Through a Proliferation-Independen…
2011
OBJECTIVE: Genetic ablation of the growth suppressor p27(Kip1) (p27) in the mouse aggravates atherosclerosis coinciding with enhanced arterial cell proliferation. However, it is unknown whether molecular mechanisms that limit p27's protective function contribute to atherosclerosis development and whether p27 exerts proliferation-independent activities in the arterial wall. This study aims to provide insight into both questions by investigating the role in atherosclerosis of p27 phosphorylation at serine 10 (p27-phospho-Ser10), a major posttranslational modification of this protein. METHODS AND RESULTS: Immunoblotting studies revealed a marked reduction in p27-phospho-Ser10 in atheroscleroti…