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)

We isolated a novel gene designated mak (male germ cell-associated kinase) by using weak cross-hybridization with a tyrosine kinase gene (v-ros). Sequence analysis of the cDNA corresponding to the 2.6-kilobase transcript revealed that the predicted product of rat mak consisted of 622 amino acids and contained protein kinase consensus motifs in its amino-terminal region. Comparison of the deduced amino acid sequence of mak in the kinase domain with those of other protein kinase genes demonstrated that mak was approximately 40% identical to the cdc2-CDC28 gene family in Schizosaccharomyces pombe, Saccharomyces cerevisiae, and humans but less identical to most other protein kinase gene products. Expression of mak was highly tissue specific, and its transcripts were detected almost exclusively in testicular cells entering and after meiosis but hardly detectable in ovarian cells including oocytes, after the dictyotene stage. These results suggest that the mak gene plays an important role in spermatogenesis.
 ...
PMID:A novel mammalian protein kinase gene (mak) is highly expressed in testicular germ cells at and after meiosis. 218 27

We have identified a novel gene encoding a putative protein kinase from a Drosophila genomic library. The gene, about 2 kbp in length, consists of four exons and codes for a protein of 349 amino acid residues. The deduced sequence shows significant similarity to various kinases, especially to a subgroup of Ser/Thr kinases related to Cdc2 kinase; thus, the gene was termed Dcdrk (Drosophila cdc2-related kinase gene). Among the kinases examined, mammalian galactosyltransferase-associated 58 kDa protein kinase showed the highest homology (about 50% identity in the kinase domain) to Dcdrk kinase. Northern blot analysis revealed that the Dcdrk mRNA is expressed throughout development in nearly constant amounts. Moreover, a whole mount in situ hybridization experiment showed that the Dcdrk mRNA is ubiquitously distributed in almost all embryonic cells and tissues, suggesting a universal function of Dcdrk, possibly in cell cycle regulation.
 ...
PMID:Identification of a novel Drosophila gene encoding a Cdc2-related protein kinase. 818 24

The recent description of a novel gene (ATM) mutated in ataxia-telangiectasia (A-T), with homologies to genes encoding proteins involved in both G1/S and G2/M checkpoint control, points to a common defect in cell cycle control in A-T operating through the cyclin-dependent kinases. In this report we demonstrate that cyclin-dependent kinases are resistant to inhibition by ionizing radiation exposure in A-T cells, and this appears to be due to insufficient induction of WAF1. Exposure of control lymphoblastoid cells to radiation during S phase and in G2 phase causes a rapid inhibition of cyclin A-Cdk2 and cyclin B-Cdc2 activities, respectively. Irradiation led to a 5-20-fold increase in Cdk-associated WAF1 in these cells, which accounts at least in part for the decrease in cyclin-dependent kinase activity. In contrast, radiation did not inhibit any of the cyclin-dependent kinase activities in S phase or G2 phase in A-T cells at short times after irradiation nor was there any significant change in the level of Cdk-associated WAF1 compared to unirradiated cells. These results are similar to those reported previously for the G1 checkpoint and provide additional evidence for the involvement of ATM at multiple points in cell cycle regulation.
 ...
PMID:Defect in multiple cell cycle checkpoints in ataxia-telangiectasia postirradiation. 870 89

The S-M checkpoint ensures that entry into mitosis is dependent on completion of DNA replication. In the fission yeast Schizosaccharomyces pombe, the SM checkpoint mutant cdc2-3w is thought to be defective in receiving the checkpoint signal. To isolate genes that function in the checkpoint pathway, we screened an S. pombe cDNA library for genes that, when overexpressed, could suppress the checkpoint defect of cdc2-3w. Using this approach, we have identified a novel gene, sum1+ (suppressor of uncontrolled mitosis). sum1+ encodes a highly conserved WD-transducin repeat protein with striking sequence similarity to the human transforming growth factor (TGF)-beta-receptor interacting protein TRIP-1 and to the translation initiation factor 3 subunit eIF3-p39, encoded by the TIF34 gene in Saccharomyces cerevisiae. S. pombe sum1+ is an essential gene, required for normal cell growth and division. In addition to restoring checkpoint control, overexpression of sum1+ inhibits the normal cell cycle response to osmotic stress. Furthermore, we demonstrate that inactivation of the stress-activated MAP kinase pathway, required for cell cycle stress response, restores the S-M checkpoint in cdc2-3w cells. These results suggest that Suml interacts with the stress-activated MAP kinase pathway and raise the possibility that environmental conditions may influence the checkpoint response in fission yeast.
 ...
PMID:Sum1, a highly conserved WD-repeat protein, suppresses S-M checkpoint mutants and inhibits the osmotic stress cell cycle response in fission yeast. 956 Mar 90

The F-box protein Skp2 is important for S phase entry and binds to Skp1 and the cyclin A-Cdk2 complex. Here we report the cloning, analysis of genomic organization and characterization of a novel gene product related to Skp2 named FBL2. The human FBL2 gene was found to be a highly interrupted gene of at least 126.6 kb located on chromosome 17 in close proximity to the TRAP220 gene in a head-to-tail orientation. The predicted protein contains an F-box and six perfect C-terminal leucine-rich repeats. Similar to Skp2, this protein interacts with Skp1 and deletion of the F-box inhibits this association. However, in contrast to Skp2, FBL2 was detected in non-proliferating hepatocytes and its expression increased in growth-arrested liver epithelial cells. In addition, FBL2 was localized primarily in the cytoplasm concentrated around the nucleus. Overall, our data indicate that although FBL2 shares strong structural homology with Skp2 as well as having a similar ability to associate with Skp1, these proteins likely play distinct roles and target different substrates to the SCF complex.
 ...
PMID:Identification of a novel Skp2-like mammalian protein containing F-box and leucine-rich repeats. 1050 20

The p16(INK4a) tumor suppressor inhibits cyclin-dependent kinases (CDK4 and CDK6). Here we report the isolation of a novel gene, SEI-1, whose product (p34(SEI-1)) appears to antagonize the function of p16(INK4a). Addition of p34(SEI-1) to cyclin D1-CDK4 renders the complex resistant to inhibition by p16(INK4a). Expression of SEI-1 is rapidly induced on addition of serum to quiescent fibroblasts, and ectopic expression of p34(SEI-1) enables fibroblasts to proliferate even in low serum concentrations. p34(SEI-1) seems to act as a growth factor sensor and may facilitate the formation and activation of cyclin D-CDK complexes in the face of inhibitory levels of INK4 proteins.
 ...
PMID:Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1). 1058 9

The Wee1 kinase inhibits entry into mitosis by phosphorylation of the Cdc2 kinase. Searching for multicopy suppressors that abolish this inhibition in the fission yeast, we have identified a novel gene, here named wos2, encoding a protein with significant homology to human p23, an Hsp90-associated cochaperone. The deletion mutant has a modest phenotype, being heat-shock sensitive. Using antibodies raised against bacterially produced protein, we determined that Wos2 is very abundant, ubiquitously distributed in the yeast cell, and its expression dropped drastically as cells entered into early stationary phase, indicating that its function is associated with cell proliferation. In proliferating cells, the amount of Wos2 protein was not subjected to cell cycle regulation. However, in vitro assays demonstrated that this Hsp90 cochaperone is potentially regulated by phosphorylation. In addition to suppressing Wee1 activity, overproduction of Wos2 displayed synthetic lethality with Cdc2 mutant proteins, indicating that this Hsp90 cochaperone functionally interacts with Cdc2. The level of Cdc2 protein and its associated H1 kinase activity under synthetic lethal conditions suggested a regulatory role for this Wos2-Cdc2 interaction. Hsp90 complexes are required for CDK regulation; the synergy found between the excess of Wos2 and a deficiency in Hsp90 activity suggests that Wos2 could specifically interfere with the Hsp90-dependent regulation of Cdc2. In vitro analysis indicated that the above genetic interactions could take place by physical association of Wos2 with the single CDK complex of the fission yeast. Expression of the budding yeast p23 protein (encoded by the SBA1 gene) in the fission yeast indicated that Wos2 and Sba1 are functionally exchangeable and therefore that properties described here for Wos2 could be of wide significance in understanding the biological function of cochaperone p23 in eukaryotic cells.
 ...
PMID:The identification of Wos2, a p23 homologue that interacts with Wee1 and Cdc2 in the mitotic control of fission yeasts. 1058 Dec 66

One novel gene product, hMAP126, was demonstrated to interact with p29 in the yeast two-hybrid assay. The full-length cDNA of hMAP126 has been obtained and encodes a protein of 1120 amino acids. Multiple tissue Northern blot analysis showed that hMAP126 was abundantly expressed in the testis. Polyclonal antiserum against hMAP126 was raised and affinity-purification of anti-hMAP126 antibodies was performed. The subcellular distribution of hMAP126 was localized to the mitotic spindle. Furthermore, hMAP126 was identified to be post-translationally modified and phosphorylated by p34(cdc2) kinase in vitro. Taken together, we have isolated a novel protein, hMAP126, which may be involved in the functional and dynamic regulation of mitotic spindles.
 ...
PMID:Cloning and characterization of hMAP126, a new member of mitotic spindle-associated proteins. 1154 62

SIC1 encodes a nonessential B-type cyclin/CDK inhibitor that functions at the G1/S transition and the exit from mitosis. To understand more completely the regulation of these transitions, mutations causing synthetic lethality with sic1 Delta were isolated. In this screen, we identified a novel gene, SID2, which encodes an essential protein that appears to be required for DNA replication or repair. sid2-1 sic1 Delta strains and sid2-21 temperature-sensitive strains arrest preanaphase as large-budded cells with a single nucleus, a short spindle, and an approximately 2C DNA content. RAD9, which is necessary for the DNA damage checkpoint, is required for the preanaphase arrest of sid2-1 sic1 Delta cells. Analysis of chromosomes in mutant sid2-21 cells by field inversion gel electrophoresis suggests the presence of replication forks and bubbles at the arrest. Deleting the two S phase cyclins, CLB5 and CLB6, substantially suppresses the sid2-1 sic1 Delta inviability, while stabilizing Clb5 protein exacerbates the defects of sid2-1 sic1 Delta cells. In synchronized sid2-1 mutant strains, the onset of replication appears normal, but completion of DNA synthesis is delayed. sid2-1 mutants are sensitive to hydroxyurea indicating that sid2-1 cells may suffer DNA damage that, when combined with additional insult, leads to a decrease in viability. Consistent with this hypothesis, sid2-1 rad9 cells are dead or very slow growing even when SIC1 is expressed.
 ...
PMID:Mutations in SID2, a novel gene in Saccharomyces cerevisiae, cause synthetic lethality with sic1 deletion and may cause a defect during S phase. 1156 Aug 84

Oral Cancer Overexpressed 1 (ORAOV1) is a novel gene locating at chromosome band 11q13. Recent studies have suggested its role as a candidate oncogene in oral squamous cell carcinoma (OSCC) and its prognostic value for patients with OSCC. Till now, the detailed function of ORAOV1 in OSCC has remained undefined. In this study, we have investigated the role of ORAOV1 in OSCC tumorigenesis by down-regulating its expression. Small interfering RNA (siRNA) has been applied to inhibit the expression of ORAOV1 in OSCC cells. We found that the OSCC cells with reduced ORAOV1 showed retarded cell growth in vitro and displayed inhibition in both tumor growth and tumor angiogenesis in vivo. Further analyses reveal that the retarded cell growth is associated with an increase in apoptosis involving the activation of caspase 3-dependent pathway and a cell cycle arrest at the S-phase with a downregulation of cyclin A, cyclin B1 and cdc2. The suppressed tumor growth in vivo may be attributed to synergistic effect between inhibition in cell growth and suppression of tumor angiogenesis. The latter is most likely because of a suppression of VEGF. Taken together, we demonstrate that ORAOV1 plays pivotal roles in the growth and angiogenesis of OSCC. Thus, ORAOV1 may be a novel target that could be explored to develop therapeutic strategy in OSCC management.
 ...
PMID:Oral cancer overexpressed 1 (ORAOV1): a regulator for the cell growth and tumor angiogenesis in oral squamous cell carcinoma. 1868 49


1 2 Next >>