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 measured the nuclear transport of radiolabeled fusion proteins consisting of variants of the Simian Virus 40 large T antigen's nuclear localization sequence region linked to beta-galactosidase, itself a cytoplasmic protein. We microinjected the fusion protein variants into the cytoplasm of living Xenopus oocytes or supplied them to the surface of oil-isolated oocyte nuclei via paired beads or cytoplasm. Presence of the cdc2 kinase site (124T) on the amino flank of the nuclear localization sequence (126PKKKRKV132) greatly enhances facilitated transport through the nuclear pore complex; additional presence of the casein kinase II site (112S) enhances subsequent intranuclear binding.
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PMID:Distinct phosphorylation sites differentially influence facilitated transport of an NLS-protein and its subsequent intranuclear binding. 750 17

We have shown previously that human cyclins A and B1 are localized differentially in the cell during interphase; cyclin A is nuclear and cyclin B1 is a cytoplasmic protein. To understand the basis of this difference we created deletion mutants and various chimeras between the two types of cyclin and expressed them in tissue culture cells by transient transfection. We find that the N-terminus of cyclin B1 contains a 42 amino acid region that is sufficient to retain the normally nuclear cyclin A in the cytoplasm. Conversely, deleting the cytoplasmic retention signal region from cyclin B1 causes the protein to become nuclear. Although the cytoplasmic retention signal region is outside the cyclin box, its sequence is well conserved in human cyclin B2, and is both necessary and sufficient to keep cyclin B2 in the cytoplasm. Thus we propose that the subcellular distribution of the B-type cyclins is determined primarily by a small region of the N-terminus which targets the cyclin--CDK complexes to particular structures in the cytoplasm.
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PMID:The differential localization of human cyclins A and B is due to a cytoplasmic retention signal in cyclin B. 807 Apr 5

The wee1 tyrosine kinase and cdc25 tyrosine phosphatase of fission yeast play antagonistic roles in the induction of mitosis through cdc2 regulation. We show here that the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis in cells expressing otherwise catastrophic levels of cdc2 activators. Paradoxically, wee1-rescued cells display very high levels of mitotic cdc2 kinase activity. We account for this anomaly by our observation that the cdc2 activator, cdc25C, is a cytoplasmic protein that, like cyclin B1, enters the nucleus at the G2/M transition. Thus, cdc2 is likely to be activated in the cytoplasm and requires nuclear localization to initiate both cytoplasmic and nuclear mitotic transformations. The human wee1 kinase appears to coordinate the transition between DNA replication and mitosis by protecting the nucleus from this cytoplasmically activated cdc2 kinase.
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PMID:Human wee1 maintains mitotic timing by protecting the nucleus from cytoplasmically activated Cdc2 kinase. 834 13

The APC gene is mutated in familial adenomatous polyposis (FAP) as well as in sporadic colorectal tumours. The product of the APC gene is a 300 kDa cytoplasmic protein associated with the adherence junction protein catenin. Here we show that overexpression of APC blocks serum-induced cell cycle progression from G0/G1 to the S phase. Mutant APCs identified in FAP and/or colorectal tumours were less inhibitory and partially obstructed the activity of the normal APC. The cell-cycle blocking activity of APC was alleviated by the overexpression of cyclin E/CDK2 or cyclin D1/CDK4. Consistent with this result, kinase activity of CDK2 was significantly down-regulated in cells overexpressing APC although its synthesis remained unchanged, while CDK4 activity was barely affected. These results suggest that APC may play a role in the regulation of the cell cycle by negatively modulating the activity of cyclin-CDK complexes.
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PMID:The tumour suppressor gene product APC blocks cell cycle progression from G0/G1 to S phase. 852 19

The cmk2 gene of Schizosaccharomyces pombe encodes a 504 amino acid protein kinase with sequence homology with the calmodulin-dependent protein kinase family. The cmk2(+) gene is not essential for cell viability but overexpression of cmk2(+) blocks the cell cycle at G2 phase and this inhibition is cdc2-dependent. The Cmk2 is a cytoplasmic protein expressed in a cell cycle-dependent manner, peaking at the G1/S boundary. Overexpression of Cmk2 suppresses fission yeast DNA replication checkpoint defects but not DNA damage checkpoint defects, suggesting that the G2 cell cycle arrest mediated by high levels of Cmk2 provides sufficient time to correct DNA replication alterations.
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PMID:Cmk2, a novel serine/threonine kinase in fission yeast. 1213 45

Saccharomyces cerevisiae ATS1 (alpha-tubulin suppressor 1) was originally identified as a high-copy suppressor of class two alpha-tubulin mutations and was proposed to have a regulatory role in coordinating the microtubule state with the cell cycle. Here, we show that Ats1p interacts with Nap1p, a cytoplasmic protein that regulates the activity of the Cdc28p/Clb2p complex. Loss of Nap1p results in a delayed switch from polar to isotropic bud growth. The delayed switch results in elongated buds. Nap1p and Ats1p interact in two-hybrid and co-immunoprecipitation assays. Both nap1Delta and ats1Delta cells have a Clb2p-dependent elongated bud morphology. Deletion of ATS1 partially suppresses the elongated bud morphology and benomyl resistance of nap1Delta mutants. Our results suggest Ats1p might regulate coordination of the microtubule state with the cell cycle through an interaction with Nap1p.
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PMID:Saccharomyces cerevisiae Ats1p interacts with Nap1p, a cytoplasmic protein that controls bud morphogenesis. 1368 Jan 56

Caldesmon (CaD) is a major actin-binding protein distributed in a variety of cell types. So far no diversity in functions of the different isoforms were found in in vitro studies. The low molecular weight isoform (Hela /-CaD) was detected in the vasculature of a variety of tumor types in our previous study. Proliferation of endothelial cells/endothelial progenitor cells (ECs/EPCs) is a crucial event for formation of new blood vessels. Here we report the intranuclear translocation of Hela /-CaD in cell cycle activated ECs/EPCs in the vasculature of human tumors. The nuclear translocation coincides with phosphorylation of the molecule and the activation of intranuclear protein kinase p34(cdc2). These findings point to a function of this molecule relating to DNA synthesis which is triggered by cell-cycle signalling pathways. The data challenge and update the generally accepted concept that CaD is a pure cytoplasmic protein in vitro study. It suggests that nuclear translocation of Hela /-CaD serves as an additional regulatory step in the control of mitotic initiation and triggers further investigations in the role of this protein in the regulation of nuclear investigations in the role of this protein in the regulation of nuclear functions.
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PMID:Hela /-CaD undergoes a DNA replication-associated switch in localization from the cytoplasm to the nuclei of endothelial cells/endothelial progenitor cells in human tumor vasculature. 1758 18