Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent work has shown that high molecular weight neurofilament (NF) proteins are phosphorylated in their carboxy-terminal tail portion by the enzyme cyclin-dependent kinase 5 (CDK-5). The tail domain of neurofilaments contains 52 tripeptide repeats, viz. Lys-Ser-Pro, which mainly exist as KSPXK and KSPXXX motifs (X = amino acid). CDK-5 specifically phosphorylates the serine residues within the KSPXK sites. We probed the structural basis for this type of substrate selectivity by studying the conformation of synthetic peptides containing either KSPXK or KSPXXX repeats designed from native neurofilament sequences. Synthetic peptides with KSPXK repeats were phosphorylated on serine with a recombinant CDK-5/p25 complex whereas those with KSPXXX repeats were unreactive in this system. Circular dichroism (CD) studies in 50% TFE/H2O revealed a predominantly helical conformation for the KSPXXX-containing peptides, whereas the CD spectra for KSPXK-containing peptides indicated the presence of a high population of extended structures in water and 50% TFE solutions. However, detailed NMR analysis of one such peptide which included two such KSPXK repeats suggested a turn-like conformation encompassing the first KSPXK repeat. Restrained molecular dynamics calculations yielded an unusually stable, folded structure with a double "S"-like bend incorporating the central residues of the peptide. The data suggest that a transient reverse turn or loop-type structure may be a requirement for CDK-5-promoted phosphate transfer to neurofilament-specific peptide segments.
 ...
PMID:Site-specific phosphorylation of Lys-Ser-Pro repeat peptides from neurofilament H by cyclin-dependent kinase 5: structural basis for substrate recognition. 953 91

Deepwater rice (Oryza sativa) is adapted to survive conditions of severe flooding over extended periods of time. During such periods adventitious roots develop to provide water, nutrients, and anchorage. In the present study the growth of adventitious roots was induced by treatment with ethylene but not auxin, cytokinin, or gibberellin. Root elongation was enhanced between 8 and 10 h after submergence. The population of cells in the S phase and expression of the S-phase-specific histone H3 gene increased within 4 to 6 h. Within 6 to 8 h the G2-phase population increased. Cell-cycle activation was accompanied by sequential induction of a cdc2-activating kinase homolog, R2, of two cdc2 genes, cdc2Os-1 and cdc2Os-2, and of three cyclin genes, cycA1;3, cycB2;1, and cycB2;2, but only induction of the R2 gene expression preceded the induction of the S phase, possibly contributing to cell-cycle regulation in the G1 phase. Both cdc2 genes were expressed at slightly higher levels during DNA replication. Transcripts of the A-type cyclin accumulated during the S and G2 phases, and transcripts of the B-type cyclins accumulated during the G2 phase. Cyclin expression was induced at all nodes with a similar time course, suggesting that ethylene acts systemically and that root primordia respond to ethylene at an early developmental stage.
 ...
PMID:Adventitious root growth and cell-cycle induction in deepwater rice 988 Mar 42

The human tyrosine phosphatase (p54(cdc25-c)) is activated by phosphorylation at mitosis entry. The phosphorylated p54(cdc25-c) in turn activates the p34-cyclin B protein kinase and triggers mitosis. Although the active p34-cyclin B protein kinase can itself phosphorylate and activate p54(cdc25-c), we have investigated the possibility that other kinases may initially trigger the phosphorylation and activation of p54(cdc25-c). We have examined the effects of the calcium/calmodulin-dependent protein kinase (CaM kinase II) on p54(cdc25-c). Our in vitro experiments show that CaM kinase II can phosphorylate p54(cdc25-c) and increase its phosphatase activity by 2.5-3-fold. Treatment of a synchronous population of HeLa cells with KN-93 (a water-soluble inhibitor of CaM kinase II) or the microinjection of AC3-I (a specific peptide inhibitor of CaM kinase II) results in a cell cycle block in G2 phase. In the KN-93-arrested cells, p54(cdc25-c) is not phosphorylated, p34(cdc2) remains tyrosine phosphorylated, and there is no increase in histone H1 kinase activity. Our data suggest that a calcium-calmodulin-dependent step may be involved in the initial activation of p54(cdc25-c).
 ...
PMID:Calcium/calmodulin-dependent phosphorylation and activation of human Cdc25-C at the G2/M phase transition in HeLa cells. 1007 93

We have investigated the spatial distributions of cell division rate, p34(cdc2) kinase activity, and amount of p34(cdc2a) in maize (Zea mays) leaves grown at contrasting temperatures and soil water conditions. An original method for calculating cell division rate in all leaf tissues is proposed. In all studied conditions, cell division rate was stable and maximum in the first 2 cm beyond the leaf insertion point, declined afterward, and reached zero at 7 cm from the insertion point. The spatial distribution of p34(cdc2) kinase activity, expressed on a per cell basis, followed the same pattern. In contrast, the amount of p34(cdc2a) was maximum in the first centimeter of the leaf, declined afterward, but remained at 20% of maximum in more distal zones with a near-zero cell division rate. A mild water deficit caused a reduction in cell division rate and p34(cdc2) kinase activity by approximately 45% in all leaf zones, but did not affect the amount of p34(cdc2a). Growth temperature affected to the same extent cell division rate and p34(cdc2) kinase activity, but only if p34(cdc2) kinase activity was assayed at growth temperature, and not if a standard temperature was used in all assays. A common linear relationship between cell division rate and p34(cdc2) kinase activity applied to all causes of changes in cell division rate, i.e. cell aging, water deficit, or changes in temperature. It is shown that temperature has two distinct and additive effects on p34(cdc2) kinase activity; first, an effect on the rate of the reaction, and second, an effect on the amount of p34(cdc2a).
 ...
PMID:Spatial distribution of cell division rate can be deduced from that of p34(cdc2) kinase activity in maize leaves grown at contrasting temperatures and soil water conditions. 1108 Mar 14

Both oil- and water-soluble allyl sulfur compounds from garlic have been found to possess antitumorigenic properties. These antitumorigenic properties increase as exposure increases both in vitro and in vivo. Generally, oil-soluble allyl sulfur compounds are more effective antiproliferative agents than their water-soluble counterparts. The ability of these compounds to suppress proliferation is associated with a depression in cell cycle progression and the induction of apoptosis. This depression in cell division coincides with an increase in the percentage of cells blocked in the G(2)/M phase of the cell cycle. A depression in p34(cdc2) kinase may account for this blockage in cell division.
 ...
PMID:Possible mechanism by which allyl sulfides suppress neoplastic cell proliferation. 1123 17

The purpose of this study was to determine whether black cohosh contains constituents that inhibit the growth of human breast cancer cells, and therefore might eventually be useful in the prevention or treatment of breast cancer. Black cohosh rhizomes were extracted with methanol/water and fractionated by solvent-solvent partitioning to yield three fractions: hexane, ethyl acetate and water. The ethyl acetate fraction displayed the highest potency in two cell-based assays, growth inhibition and cell cycle analysis. This fraction inhibited growth of both the ER+ MCF7 and ER-MDA-MB-453 human breast cancer cell lines with IC50 values of about 20 and 10 micro g/ml, respectively. It also induced cell cycle arrest at G1 when tested at 30 micro g/ml and at G2/M at 60 micro g/ml in MCF7 cells. This suggests that the extract contains a mixture of components with the more active (or more abundant) causing G1 arrest and the less active causing G2/M arrest. We then examined specific components in this extract. The triterpene glycoside fraction obtained by polyamide column chromatography, and the specific triterpene glycosides actein, 23-epi-26-deoxyactein and cimiracemoside A, inhibited growth of the MCF7 human breast cancer cells and induced cell cycle arrest at G1. The most potent compound, actein, decreased the level of cyclin D1, cdk4 and the hyperphosphorylated form of the pRb protein and increased the level of p21cip1 in MCF7 cells, changes that may contribute to the arrest in G1. Further studies are in progress to identify the mechanisms by which actein and related compounds present in black cohosh inhibit growth of human breast cancer cells.
 ...
PMID:Growth inhibitory activity of extracts and purified components of black cohosh on human breast cancer cells. 1475 92

Scutellaria barbata D. Don (SB) is one of the herbs belonging to perennial plants, which is known in traditional Korean medicine as 'Ban-Ji-Ryun,' and has been used as an anti-inflammatory and anti-tumor agents against human uterine leiomyoma, mammalian and ovarian cancers. Although the difference between uterine smooth muscle cell (SMC) and leiomyomal SMCs has not been clearly established, the action of SB water extract was investigated using SMCs from normal myometrium and leiomyoma. The proliferation of cultured myometrial and leiomyomal SMC was inhibited by SB treatment. Flow cytometric analysis showed that the population in the G1 phase of the cell cycle increased under SB treatment. Western blotting analysis showed that markers of SMC differentiation such as alpha-smooth muscle actin (alpha-SMA), calponin h1 and cyclin-dependent kinase inhibitor p27 were induced by treatment with SB in myometrial and leiomyomal SMCs. In contrast, cell-cycle-related gene products from the G1 phase of the cell cycle, such as cyclin E and cdk2, were not affected. Taken together, these results indicate that SB inhibits the proliferation of myometrial and leiomyomals SMC through the induction of alpha-SMA, calponin h1 and p27. It is suggested that SB may induce differentiation in uterine SMC and may influence tissue remodeling and reconstruction during physiological and pathophysiological events.
 ...
PMID:Inhibitory effects of Scutellaria barbata D. Don on human uterine leiomyomal smooth muscle cell proliferation through cell cycle analysis. 1507 97

Scutellaria barbata D. Don (Lamiaceae)(SB) is a perennial herb which is natively distributed throughout Korea and southern China. This herb is known in traditional Chinese Medicine as Ban-Zhi-Lian and traditional Korean medicine as Banjiryun, respectively. SB has been used as an anti-inflammatory and antitumor agent. We aimed to determine the expressin of cell cycle-related signal molecules for growth inhibition after HCG treatment by the herb SB in two different human myometrial smooth muscle cells (SMCs) and leiomyomal SMCs. Water-soluble ingredients of SB, myometrial SMCs and the leiomyomal cell lines were used in vitro. Uterine myomas often enlarge rapidly during pregnancy, implying that human chorionic gonadotrophin (HCG) may influences cell proliferation in uterine leiomyomata. We investigated the effects of SB on the cell proliferation and the expression of cell cycle-related proteins in these cells. Although HCG/LH receptor was present in both cultured myometrial and leiomyomal cells, as assayed by reverse transcription polymerase chain reaction analysis, treatment with HCG significantly increased cell proliferation in both myometrial and leiomyomal cells. However, SB reduced the proliferative effect of HCG in leiomyoma and myometrial cells, respectively. In HCG-treated leiomyomal cells, the expression of proliferating cell nuclear antigen, cyclin E and cdc2 was significantly reduced by SB treatment. These results suggest that SB reduced the HCG-promoted proliferation of myometrial and leiomyomal cells.
 ...
PMID:Differential inhibition of Scutellaria barbata D. Don (Lamiaceae) on HCG-promoted proliferation of cultured uterine leiomyomal and myometrial smooth muscle cells. 1551 68

The antitumor activity of the crude water extract from Gac fruit (Momordica cochinchinensis) was investigated in vivo and in vitro. A water extract prepared from 0.75 and 0.25 mg dry weight of Gac fruit per gram body weight was given daily to Balb/c mice (n=15/group). The water extract inhibited the growth of the colon 26-20 adenocarcinoma cell line, transplanted in Balb/c mice, reducing wet tumor weight by 23.6%. Histological and immunohistochemical results indicated that Gac water extract reduced the density of blood vessels around the carcinoma. The water extract also produced a marked suppression of cell proliferation in colon 26-20 and HepG2 cells. Cell cycle analysis demonstrated a significant accumulation of cells in the S phase by water extract. Immunoblotting showed that cyclin A, Cdk2, p27waf1/Kip1 were down-regulated, whereas the protein level of p21waf1/Cip1 was not decreased. Treatment of colon 26-20 cells with Gac extract induced necrosis rather than apoptosis. The antitumor component was confirmed as a protein with molecular weight of 35 kDa, retained in the water-soluble high molecular weight fraction. Thus, the bioactive antitumor compound in Gac extract is a protein, which is distinct from lycopene, another compound in Gac fruit with potential antitumor activity.
 ...
PMID:Inhibition of tumor growth and angiogenesis by water extract of Gac fruit (Momordica cochinchinensis Spreng). 1575 81

Eight genes showed significant changes in expression in mice under psychophysiological stress provided by cage-restraint and water-immersion. The transcription level of most of these genes was affected in all the tissues analyzed, and some of them were responsive genes in several different stress systems. Peculiarly, the expression level of one gene, cdc2-like kinase 1 (CLK1), was reduced only in the brain, while the balance of partially- and alternatively-spliced CLK1 mRNA species changed in all the tissues including the brain. These results suggest that some stress-response mechanisms, including transcriptional and post-transcriptional events, are coordinated in the whole body in mice under psychophysiological stress.
 ...
PMID:Psychophysiological stress-regulated gene expression in mice. 1581 31


1 2 3 4 Next >>