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

The pancreatic cell line beta TC1, established from insulinomas of transgenic mice carrying a hybrid insulin-promoted large T antigen gene, has retained several characteristics of normal cells, including the insulin content and inducibility of insulin secreting by glucose. We show here that the growth of beta TC1 cells is arrested in low serum-concentration medium. Cells exposed for three days to 0.25% fetal calf serum ceased to incorporate [3H]thymidine but were still able to resume the cell division cycle upon addition of serum. In this cell line, we have determined by cytofluorometry the cell cycle kinetic parameters to be of 21 h, 10 h 30 min and 12 h for the G1, S and G2/M phases, respectively. Quiescent beta TC1 cells constitutively expressed the protooncogene c-jun that codes for the transcriptional factor AP1, as well as cdc2, another cell cycle-related gene. A large transient increase in the expression of the c-fos gene was obtained rapidly, 30 min after addition of serum and a similar increase in c-jun expression after one hour. Expression of the cdc2 gene was also enhanced to a lesser extent. The same effects were also observed in the presence of cycloheximide, thus proving that the expression of these three genes is directly stimulated by serum growth factors. Consequently, quiescent beta TC1 cells provide a good model for studying the short- and long-term effects of growth factors on Beta-cell proliferation.
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PMID:Cell cycle and gene expression in the insulin producing pancreatic cell line beta TC1. 170 44

G1 cyclins and some cyclin-dependent kinases (cdks) have been implicated in the G1/S transition during the eukaryotic cell cycle initiation. The present study demonstrates that the genes of cyclin E, cdk2, cdk5 and the transcriptional factor E2F-1 are expressed during the prolactin (PRL)-induced G1/S transition in rat Nb2 pre-T lymphoma cells. The mRNAs for these four cell cycle regulators were synergistically synthesized and degraded after the stimulation by PRL. The maximal levels of these mRNAs were observed at 8 to 12 h after the PRL addition, while DNA replication reached to the maximum between 12 and 16 h. These results suggest that cyclin E, cdk2, cdk5 and E2F-1 play the roles in the G1/S transition being expressed by a common cellular mechanism(s) in the PRL-stimulated pre-T lymphoma cells.
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PMID:Synergistic gene expressions of cyclin E, cdk2, cdk5 and E2F-1 during the prolactin-induced G1/S transition in rat Nb2 pre-T lymphoma cells. 867 24

Curcumin (CCM), a major yellow pigment of turmeric obtained from powdered rhizomes of the plant Curcuma longa Linn, is commonly used as coloring agent in foods, drugs and cosmetics. In this study we report that gavage administration of 200 mg/kg or 600 mg/kg CCM effectively suppressed diethylnitrosamine (DEN)-induced liver inflammation and hyperplasia in rats, as evidenced by histopathological examination. Immunoblotting analysis showed that CCM strongly inhibited DEN-mediated the increased expression of oncogenic p21(ras) and p53 proteins in liver tissues of rats. In cell-cycle-related proteins, CCM selectively reduced the expression of proliferating cell nuclear antigen (PCNA), cyclin E and p34(cdc2), but not Cdk2 or cyclin D1. Moreover, CCM also inhibited the DEN-induced increase of transcriptional factor NF-kappa B. However, CCM failed to affect DEN-induced c-Jun and c-Fos expression. It has become widely recognized that the development of human hepatocellular carcinoma (HCC) is predominantly due to the chronic inflammation by virus, bacteria or chemical. Our results suggest a potential role for CCM in the prevention of HCC.
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PMID:Inhibition by curcumin of diethylnitrosamine-induced hepatic hyperplasia, inflammation, cellular gene products and cell-cycle-related proteins in rats. 1103 36

In herpes simplex virus 1-infected cells, a high level of alpha gene expression requires the transactivation of the genes by a complex containing the viral alpha transinducing factor (alphaTIF) and two cellular proteins. The latter two, HCF-1 and octamer binding protein Oct-1, are transcriptional factors regulated in a cell cycle-dependent manner. alphaTIF is a protein made late in infection but packaged with the virion to transactivate viral genes in newly infected cells. In light of the accumulation of large amounts of alphaTIF, the absence of alpha gene expression late in infection suggested the possibility that one or more transcriptional factors required for alpha gene expression is modified late in infection. Here we report that Oct-1 is posttranscriptionally modified late in infection, that the modification is mediated by the virus but does not involve viral protein kinases or cdc2 kinase activated by the virus late in infection, and that the modified Oct-1 has a reduced affinity for its cognate DNA site. These results are consistent with the hypothesis that modification of Oct-1 transcriptional factor could account at least in part for the shutoff of alpha gene expression late in infection.
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PMID:Oct-1 is posttranslationally modified and exhibits reduced capacity to bind cognate sites at late times after infection with herpes simplex virus 1. 1458 29

CCAAT enhancer-binding protein (C/EBP)beta is a basic leucine zipper transcription factor family member, and can be phosphorylated, acetylated, and sumoylated. C/EBPbeta undergoes sequential phosphorylation during 3T3-L1 adipocyte differentiation. Phosphorylation on Thr(188) by MAPK or cyclin A/cdk2 primes the phosphorylations on Ser(184)/Thr(179) by GSK3beta, and these phosphorylations are required for the acquisition of DNA binding activity of C/EBPbeta. Here we show that C/EBPbeta is modified by O-GlcNAc, a dynamic single sugar modification found on nucleocytoplasmic proteins. The GlcNAcylation sites are Ser(180) and Ser(181), which are in the regulation domain and are very close to the phosphorylation sites (Thr(188), Ser(184), and Thr(179)) required for the gain of DNA binding activity. Both in vitro and ex vivo experiments demonstrate that GlcNAcylation on Ser(180) and Ser(181) prevents phosphorylation on Thr(188), Ser(184), and Thr(179), as indicated by the decreased relative phosphorylation and DNA binding activity of C/EBPbeta delayed the adipocyte differentiation program. Mutation of both Ser(180) and Ser(181) to Ala significantly increase the transcriptional activity of C/EBPbeta. These data suggest that GlcNAcylation regulates both the phosphorylation and DNA binding activity of C/EBPbeta.
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PMID:O-linked N-acetylglucosamine modification on CCAAT enhancer-binding protein beta: role during adipocyte differentiation. 1947 79

Snail is a multifunctional transcriptional factor that has been described as a repressor in many different contexts. It is also proposed as an activator in a few cases relevant to tumor progression and cell-cycle arrest. This study investigated the detailed mechanisms by which Snail upregulates gene expression of the CDK inhibitor p15(INK4b) in HepG2 induced by the tumor promoter tetradecanoyl phorbol acetate (TPA). Using deletion mapping, the TPA-responsive element on the p15(INK4b) promoter was located between 77 and 228 bp upstream of the transcriptional initiation site, within which the putative binding regions of early growth response gene 1 (EGR-1) and stimulatory protein 1 (SP-1) were found. Gene expression of EGR-1, Snail and SP-1 can be induced by TPA within 0.5-6 h. In addition, basal levels of SP-1, but not of the other two transcriptional factors, were observed. Blockade of TPA-induced gene expression of Snail, EGR-1 or SP-1 suppressed activation of the p15-pro228 reporter plasmid harboring the TPA-responsive element. More detailed deletion mapping and site-directed mutagenesis further concluded that the overlapping EGR-1/SP-1-binding site was required for TPA-induced p15-pro228 activation. In an EMSA, a DNA-protein complex was elevated by TPA, which can be blocked by antibodies against EGR-1, SP-1 or Snail at 6 h. Immunoprecipitation/western blotting demonstrated that TPA could trigger the association of EGR-1 with Snail or SP-1. Furthermore, a double chromatin immunoprecipitation assay verified that EGR-1 could form a complex with Snail or SP-1 on the TPA-responsive element after treatment with TPA for 2-6 h. Finally, we demonstrated a novel Snail-target region which could be bound by Snail and was also required for TPA-induced p15-pro228 activation. In conclusion, Snail associates with EGR-1 and SP-1 to mediate TPA-induced transcriptional upregulation of p15(INK4b) in HepG2.
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PMID:Snail associates with EGR-1 and SP-1 to upregulate transcriptional activation of p15INK4b. 2012 49

Idiopathic pulmonary fibrosis (IPF) is a prevalent, progressive, and incurable fibroproliferative lung disease. The phenotype of IPF fibroblasts is characterized by their ability to elude the proliferation-suppressive properties of polymerized type I collagen. The mechanism underlying this pathological response is incompletely understood but involves aberrant activation of the phosphatidylinositol 3-kinase-Akt signaling pathway owing to inappropriately low phosphatase and tensin homolog phosphatase activity. Akt can phosphorylate and inactivate the forkhead box O3a (FoxO3a) transcriptional factor, which, when transcriptionally active, increases the expression of the CDK inhibitor p27 and promotes cell cycle arrest. Herein, we demonstrate that IPF fibroblasts display high levels of inactive FoxO3a compared with nonfibrotic control fibroblasts because of their high Akt activity. We found that p27 levels are decreased in IPF compared with control fibroblasts cultured on polymerized collagen. Furthermore, overexpression of FoxO3a in IPF fibroblasts increases p27 levels and suppresses the ability of IPF fibroblasts to proliferate on polymerized collagen. In contrast, the expression of dominant-negative FoxO3a augmented control fibroblast proliferation. IHC examination of fibroblastic foci in IPF lung tissue demonstrates the presence of inactive FoxO3a in cells within fibroblastic foci. These data indicate that the ability of IPF fibroblasts to circumvent the proliferation-suppressive properties of polymerized collagen involves inactivation of FoxO3a by high Akt activity, resulting in down-regulation of p27.
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PMID:Pathological alteration of FoxO3a activity promotes idiopathic pulmonary fibrosis fibroblast proliferation on type i collagen matrix. 2189 17

Cdc6 is the bifunctional AAA+ ATPase that assembles prereplicative complexes on origins of replication and activates p21(CIP1)- or p27(KIP1)-bound Cdk2. During the G(1)-S transition, the Cdc6 gene essential for chromosomal replication is activated by the E2F transcriptional factor. Paradoxically, Apaf-1 encoding the central component of the apoptosome is also activated at the same time and by E2F. Consequently, genes for antipodal life and death are regulated in the same manner by the same transcriptional factor. Here we report a striking solution to this paradox. Besides performing prereplicative complex assembly and Cdk2 activation, Cdc6 obstructed apoptosome assembly by forming stable complexes very likely with a monomer of cytochrome c-activated Apaf-1 molecules. This function depended on its own ATPase domain but not on the cyclin-binding motif. In proliferating rodent fibroblasts, Cdc6 continued to block apoptosome assembly induced by a non-cytochrome c or some other mechanism, suppressing seemingly unintended apoptosis when promoting cell proliferation. Thus, Cdc6 is an AAA+ ATPase with three functions, all working for life.
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PMID:Cdc6 protein obstructs apoptosome assembly and consequent cell death by forming stable complexes with activated Apaf-1 molecules. 2568 11