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Cell Division Cycle (cell + division_cycle)
Selected AbstractsGene expression profiles associated with aging and mortality in humansAGING CELL, Issue 3 2009Richard A. Kerber Summary We investigated the hypothesis that gene expression profiles in cultured cell lines from adults, aged 57,97 years, contain information about the biological age and potential longevity of the donors. We studied 104 unrelated grandparents from 31 Utah CEU (Centre d'Etude du Polymorphisme Humain , Utah) families, for whom lymphoblastoid cell lines were established in the 1980s. Combining publicly available gene expression data from these cell lines, and survival data from the Utah Population Database, we tested the relationship between expression of 2151 always-expressed genes, age, and survival of the donors. Approximately 16% of 2151 expression levels were associated with donor age: 10% decreased in expression with age, and 6% increased with age. Cell division cycle 42 (CDC42) and CORO1A exhibited strong associations both with age at draw and survival after draw (multiple comparisons-adjusted Monte Carlo P -value < 0.05). In general, gene expressions that increased with age were associated with increased mortality. Gene expressions that decreased with age were generally associated with reduced mortality. A multivariate estimate of biological age modeled from expression data was dominated by CDC42 expression, and was a significant predictor of survival after blood draw. A multivariate model of survival as a function of gene expression was dominated by CORO1A expression. This model accounted for approximately 23% of the variation in survival among the CEU grandparents. Some expression levels were negligibly associated with age in this cross-sectional dataset, but strongly associated with inter-individual differences in survival. These observations may lead to new insights regarding the genetic contribution to exceptional longevity. [source] 13C-Labeled metabolic flux analysis of a fed-batch culture of elutriated Saccharomyces cerevisiaeFEMS YEAST RESEARCH, Issue 4 2007Roeland Costenoble Abstract This study addresses the question of whether observable changes in fluxes in the primary carbon metabolism of Saccharomyces cerevisiae occur between the different phases of the cell division cycle. To detect such changes by metabolic flux analysis, a 13C-labeling experiment was performed with a fed-batch culture inoculated with a partially synchronized cell population obtained through centrifugal elutriation. Such a culture exhibits dynamic changes in the fractions of cells in different cell cycle phases over time. The mass isotopomer distributions of free intracellular metabolites in central carbon metabolism were measured by liquid chromatography,mass spectrometry. For four time points during the culture, these distributions were used to obtain the best estimates for the metabolic fluxes. The obtained flux fits suggested that the optimally fitted split ratio for the pentose phosphate pathway changed by almost a factor of 2 up and down around a value of 0.27 during the experiment. Statistical analysis revealed that some of the fitted flux distributions for different time points were significantly different from each other, indicating that cell cycle-dependent variations in cytosolic metabolic fluxes indeed occurred. [source] Schizosaccharomyces pombe cell division cycle under limited glucose requires Ssp1 kinase, the putative CaMKK, and Sds23, a PP2A-related phosphatase inhibitorGENES TO CELLS, Issue 5 2009Yuichiro Hanyu Calcium/calmodulin-dependent protein kinase (CaMK) is required for diverse cellular functions, and similar kinases exist in fungi. Although mammalian CaMK kinase (CaMKK) activates CaMK and also evolutionarily-conserved AMP-activated protein kinase (AMPK), CaMKK is yet to be established in yeast. We here report that the fission yeast Schizosaccharomyces pombe Ssp1 kinase, which controls G2/M transition and response to stress, is the putative CaMKK. Ssp1 has a CaM binding domain (CBD) and associates with 14-3-3 proteins as mammalian CaMKK does. Temperature-sensitive ssp1 mutants isolated are defective in the tolerance to limited glucose, and this tolerance requires the conserved stretch present between the kinase domain and CBD. Sds23, multi-copy suppressor for mutants defective in type 1 phosphatase and APC/cyclosome, also suppresses the ssp1 phenotype, and is required for the tolerance to limited glucose. We demonstrate that Sds23 binds to type 2A protein phosphatases (PP2A) and PP2A-related phosphatase Ppe1, and that Sds23 inhibits Ppe1 phosphatase activity. Ssp1 and Ppe1 thus seem to antagonize in utilizing limited glucose. We also show that Ppk9 and Ssp2 are the catalytic subunits of AMPK and AMPK-related kinases, respectively, which bind to common ,-(Amk2) and ,-(Cbs2) subunits. [source] Effects of histone deacetylase inhibitors on p55CDC/Cdc20 expression in HT29 cell lineJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2006Giuseppe Iacomino Abstract In a previous work, taking advantage of the gene-array screening technology, we analysed the effects of histone deacetylase (HDAC) inhibitor sodium butyrate (NaBt), on gene transcription in HT29 human adenocarcinoma cell line. In this study, we focused our attention on p55CDC/Cdc20 gene, whose expression was dramatically reduced by NaBt treatment. Mammalian p55CDC/Cdc20 interacts with the anaphase promoting complex/cyclosome (APC/C), and is involved in regulating anaphase onset and late mitotic events. Using NaBt and trichostatin A (TSA), a member of the HDAC inhibitor family, we showed that both HDAC inhibitors totally downregulated p55CDC/Cdc20 transcription and expression. Cell cycle analysis demonstrated that NaBt arrested HT29 cells in G0/G1 phase, while TSA caused a double block in G0/G1 and G2/M phases. Moreover, p55CDC/Cdc20 showed maximal expression in S and G2/M phases of HT29 cell division cycle. Based on this evidence, and by means of specific cell cycle modulators, such as nocodazole and hydroxyurea, we demonstrated that both TSA and NaBt were responsible for loss of p55CDC/Cdc20 expression, but with different mechanisms of action. Taken together, these results suggest that targeting molecules involved in spindle mitotic checkpoint, such as p55CDC/Cdc20, might account for the high cytotoxicity of HDAC inhibitors versus malignant cells. J. Cell. Biochem. 99: 1122,1131, 2006. © 2006 Wiley-Liss, Inc. [source] BIOCHEMISTRY OF SILICA BIOMINERALIZATION IN DIATOMSJOURNAL OF PHYCOLOGY, Issue 2000M. Sumper Diatoms are well known for the intricate patterns of their silica-based cell walls. The complex structures of diatom cell walls are species specific and become precisely reproduced during each cell division cycle, indicating a genetic control of silica biomineralization. Therefore, the formation of the diatom cell wall has been regarded as a paradigm for controlled production of nanostructured silica. However, the mechanisms allowing biosilicification to proceed at ambient temperature at high rates have remained enigmatic. Recently, we have shown that a set of highly cationic peptides (called silaffins) isolated from Cylindrotheca fusiformis shells are able to generate networks of silica nanospheres within seconds when added to a solution of silicic acid. Different silaffin species produce different morphologies of the precipitated silica. Silaffins contain covalently modified Lys-Lys elements. One of these lysine residues bears a novel type of protein modification, a polyamine consisting of 6,11 repeats of the N-methyl-propylamine unit. In addition to the silaffins, additional polyamine-containing substances have been isolated from a number of diatom species that may be involved in the control of biosilica morphology. Scanning electron microscopic analysis of diatom shells isolated in statu nascendi provide insights into the processes of pattern formation in biosilica. A model will be discussed that explains production of nanostructured biosilica in diatoms on the basis of these experimental results. [source] New established melanoma cell lines: genetic and biochemical characterization of cell division cycleJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2003A Vozza ABSTRACT Background Cancer might be envisaged as the result of a genetic process causing the unregulated proliferation of a given cell as well as its inability to undergo differentiation and/or apoptosis. Alterations of genes regulating cell division cycle appear to play a key role in the development of human cancer. Objective On the bases of the above considerations, we decided to establish new cell lines from human melanoma specimens, in order to analyse the molecular alterations in primary preparations of malignant cells. Results The present paper describes two new established cell lines and their genetic and biochemical features. Both the melanoma cell lines show inactivation of the cyclin-dependent kinase inhibitor gene, CDKN2A/p16INK4A, thus demostrating that this alteration occurs in primary human melanomas. No other alterations were observable when we investigated several different cell cycle genes including those encoding cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors. Analyses at protein level by means of immunoblotting confirmed the results obtained at the genetic level. Moreover, the inducibility of a pivotal cyclin-dependent kinase inhibitor gene, namely p21CIP1 gene, was obtained by treating the cells with histone deacetylase inhibitors, namely butyrate and phenylbutyrate. Conclusions Our results suggest a primary role of cyclin-dependent kinase inhibitor genes inactivation in the origin of human melanoma and allow the proposal of new therapeutic strategies based on the transcriptional activation of p21CIP1 gene. [source] Flavonoids as RTK inhibitors and potential anticancer agentsMEDICINAL RESEARCH REVIEWS, Issue 5 2008Florence Teillet Abstract Tyrosine kinase receptors (RTKs) play a crucial role in the regulation of the cell division cycle. Currently more than 50 RTKs divided into several subfamilies have been described. The inhibition of these enzymes has emerged as an important research-area. Compounds able to inhibit the activity of these enzymes are expected to display antiproliferative properties. Flavonoids are representative of various small molecules acting as RTK inhibitors. These naturally occurring compounds are able to bind to the ATP-binding site of several kinases. The most plausible current hypothesis explaining the action of these substances on kinases is that the chromenone moiety of the flavonoid acts as a mimetic of the adenine moiety of ATP, the receptor co-factor. In this review, we report recent results on the activity of natural and synthetic derivatives of flavonoids as inhibitors of RTKs. Mechanistic aspects, the therapeutic usefulness, and the potential clinical use are discussed. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 5, 715,745, 2008 [source] Inhibition of proteasome-dependent degradation of Wee1 in G2 -arrested Hep3B cells by TGF,1MOLECULAR CARCINOGENESIS, Issue 4 2003Osamu Hashimoto Abstract Transforming growth factor ,1 (TGF,1)-induced G2 arrest was observed when a proliferation inhibitory function of the retinoblastoma protein (Rb) was compromised, but the mechanism underlying the G2 arrest was poorly characterized compared with that of G1 arrest. In the present study, we characterized G2 arrest induced by TGF,1 (1 ng/mL) in the Rb-negative hepatoma cell line (Hep3B) and compared with G1 arrest in the Rb-positive hepatoma cell line (Huh7). Activities of cyclin-dependent kinases (CDK) 2 and cell division cycle (CDC) 2 were markedly decreased at 24 h, the time when cell-cycle arrest became apparent in both cell lines. However, considerable amounts of inactive CDC2-cyclinB1 complexes were present in the nucleus of G2 -arrested Hep3B but were not present in G1 -arrested Huh7. The inhibitory phosphorylation of CDC2 on Tyr-15 was significantly elevated at 12,24 h, and its levels gradually declined during G2 arrest in Hep3B. In particular, augmentation of CDK inhibitors p21cip1 and p27kip1 and Wee1 kinase and diminution of CDC25C phosphatase coincided with induced Tyr-15 phosphorylation and inhibition of CDC2. Wee1 in Hep3B was unstable and was degraded in a proteasome-dependent manner, but it became substantially stabilized within 6 h of TGF,1 treatment. Moreover, a Wee1 inhibitor, PD0166285, abrogated the TGF,1-induced G2 arrest in Hep3B. These findings suggest that TGF,1 induced G2 arrest in Hep3B at least in part through stabilization of Wee1 and subsequent increase in Tyr-15 phosphorylation and inhibition of CDC2. © 2003 Wiley-Liss, Inc. [source] Many but not all Genes in Chlamydomonas reinhardtii are Regulated by the Circadian ClockPLANT BIOLOGY, Issue 6 2001S. Jacobshagen Abstract: Total RNA from autotrophic Chlamydomonas reinhardtii cultures grown in constant dim light and 17 °C constant temperature was subjected to Northern blot analyses. The mRNAs for cytochrome c, ,-tubulin, HSP70B (a chloroplastic heat shock protein of the 70 kD family), chloroplastic fructose-bisphosphate aldolase, and GAS3 (a "gamete-specific" protein of unknown function with high expression in gametes but low expression in vegetative cells) each exhibit a clear circadian rhythm in abundance. The rhythms differ significantly in phase and amplitude. The findings show that the genes for cytochrome c and ,-tubulin indeed are regulated by the circadian clock, as previously suggested. Experiments with cultures grown at 27 °C instead of 17 °C further revealed that the rhythms in mRNA abundance for HSP70B, chloroplastic aldolase, and GAS3 also occur with a similar period at the higher temperature. Thus, the rhythms conform to the criterion of temperature compensation for the period and therefore represent true circadian rhythms. In contrast, the combined amount of mRNA for ubiquitin 52 amino acid fusion protein and ubiquitin 78 to 81 amino acid fusion protein stays constant under both temperature conditions. Because the combined amount of mRNA for the ubiquitin fusion proteins was previously shown to cycle under diurnal conditions when cell division activity is high, our data suggest a regulation of these genes by the cell division cycle and not the circadian clock. In summary, our data, together with several other reports, suggest that the circadian clock regulates many but not all genes in Chlamydomonas reinhardtii. [source] Influence on antiproliferative activity of structural modification and conjugation of gonadotropin-releasing hormone (GnRH) analoguesCELL PROLIFERATION, Issue 5 2000A. Kálnay Abstract The effect of various GnRH analogues, and their conjugates on proliferation, clonogenicity and cell cycle phase distribution of MCF-7 and Ishikawa human cancer cell lines was studied. GnRH-III, a sea lamprey GnRH analogue reduced cell proliferation by 35% and clonogenicity by 55%. Structural modifications either decreased, or did not alter biological activity. Conjugation of GnRH analogues including MI-1544, MI-1892, and GnRH-III with poly(N-vinylpyrrolidone-co-maleic acid) (P) through a tetrapeptide spacer GFLG(X) substantially increased the inhibitory effect of the GnRH analogues. The conjugate P-X-GnRH-III induced significant accumulation of cells in the G2/M phase; from 8% to 15.6% at 24 h and 9.8% to 15% at 48 h. It was concluded that conjugation of various GnRH analogues substantially enhanced their antiproliferative activity, strongly reduced cell clonogenicity and retarded cell progression through the cell division cycle at the G2/M phase. [source] ATP-Noncompetitive Inhibitors of CDK,Cyclin ComplexesCHEMMEDCHEM, Issue 1 2009Mar Orzáez Dr. Abstract Progression through the cell division cycle is controlled by a family of cyclin-dependent kinases (CDKs), the activity of which depends on their binding to regulatory partners (cyclins A,H). Deregulation of the activity of CDKs has been associated with the development of infectious, neurodegenerative, and proliferative diseases such as Alzheimer's, Parkinson's, or cancer. Most cancer cells contain mutations in the pathways that control the activity of CDKs. This observation led this kinase family to become a central target for the development of new drugs for cancer therapy. A range of structurally diverse molecules has been shown to inhibit the activity of CDKs through their activity as ATP antagonists. Nevertheless, the ATP binding sites on CDKs are highly conserved, limiting the kinase specificity of these inhibitors. Various genetic and crystallographic approaches have provided essential information about the mechanism of formation and activation of CDK,cyclin complexes, providing new ways to implement novel research strategies toward the discovery of new, more effective and selective drugs. Herein we review the progress made in the development of ATP-noncompetitive CDK,cyclin inhibitors. [source] | ||||||||||||||||