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  • Cdk2
  • Additionally, we develop a chemical genetic approach that allows for the selective inhibition of Cdk2 in multiple cell and cancer types. (proquest.com)
  • In an independent project, we use a chemical-genetic approach to achieve selective inhibition of Cdk2 kinase activity using an analog sensitive (AS) allele. (proquest.com)
  • We show that inhibition of Cdk2 kinase activity slows proliferation of non-transformed cells, whereas siRNA knockdown of Cdk2 does not, highlighting the differences between these approaches. (proquest.com)
  • We also show that Cdk2 inhibition attenuates anchorage-independent growth of transformed cells. (proquest.com)
  • Finally, we develop a Cdk2-AS mouse model that will allow for the acute inhibition of Cdk2 in a variety of cell types and cancer models. (proquest.com)
  • Cyclin A-CDK2 complex is present in G2 phase. (biotecharticles.com)
  • This cyclin binds both Cdk1 and Cdk2 kinases, which give two distinct kinase activities, one appearing in S phase, the other in G2, and thus regulate separate functions in cell cycle. (wikipedia.org)
  • The role of this protein in G1-S transition has been recently questioned as cells lacking Cdk2 are reported to have no problem during this transition. (wikipedia.org)
  • Drugs that inhibit Cdk2 and arrest the cell cycle, such as GW8510 and the experimental cancer drug seliciclib, may reduce the sensitivity of the epithelium to many cell cycle-active antitumor agents and, therefore, represent a strategy for prevention of chemotherapy-induced alopecia. (wikipedia.org)
  • P27 can also be regulated by changing its subcellular location Both mechanisms act to reduce levels of p27, allowing for the activation of Cdk1 and Cdk2, and for the cell to begin progressing through the cell cycle. (wikipedia.org)
  • SKP1 and Skp2 degrades p27 after it has been phosphorylated at threonine 187 (Thr187) by either activating cyclin E- or cyclin A-CDK2. (wikipedia.org)
  • Oncogene
  • Background: The Ret proto-oncogene (c-Ret) is a receptor tyrosine kinase that functions as a multicomponent receptor complex in conjunction with other membrane-bound, ligand-binding GDNF family receptors (1). (cellsignal.com)
  • CDC2
  • The encoded protein directs dephosphorylation of cyclin B-bound CDC2 and triggers entry into mitosis. (nih.gov)
  • This covalent modification of the molecular structure of Cdc2 inhibits the enzymatic activity of Cdc2 and prevents cell division. (wikipedia.org)
  • Wee1 acts to keep Cdc2 inactive during early G2 when cells are still small. (wikipedia.org)
  • It has been shown in Wee1 mutants, cells with weakened Wee1 activity, that Cdc2 becomes active when the cell is smaller. (wikipedia.org)
  • substrates
  • In biochemistry, a kinase is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. (wikipedia.org)
  • Yet, few in vivo substrates linking CDK activity with the promotion of particular events in the cell cycle have been characterised. (biologists.org)
  • Furthermore, cyclin binding determines the specificity of the cyclin-CDK complex for particular substrates. (wikipedia.org)
  • At least some cyclins contain a hydrophobic patch which may directly interact with substrates, conferring target specificity. (wikipedia.org)
  • CDK6
  • There are additional functions of CDK6 not associated with its kinase activity. (wikipedia.org)
  • For example, CDK6 is involved in the differentiation of T cells, acting as an inhibitor of differentiation. (wikipedia.org)
  • CDK6 has also been found to be important in the development of other cell lines, for example, CDK6 has a role in the alteration of the morphology of astrocytes and in the development of other stem cells. (wikipedia.org)
  • Studies in the metabolic control of cells have revealed yet another role of CDK6. (wikipedia.org)
  • Proliferation
  • Downregulation of cell division cycle 25 homolog C reduces the radiosensitivity and proliferation activity of esophageal squamous cell carcinoma. (nih.gov)
  • Embryonic stem (ES) cells are an attractive source for stem cell therapies due to their rapid proliferation and capacity for differentiation. (proquest.com)
  • This is not to be confused with growth in the context of cell division, referred to as proliferation, where a cell, known as the "mother cell", grows and divides to produce two "daughter cells" (M phase). (wikipedia.org)
  • In mouse embryonic stem cells (ESCs), Cdc7 is needed for proliferation. (wikipedia.org)
  • This kinase has been shown to play a role in cellular proliferation. (wikipedia.org)
  • Wee1
  • This suggests that cell division may be regulated in part by dilution of Wee1 protein in cells as they grow larger. (wikipedia.org)
  • Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe (S. pombe). (wikipedia.org)
  • Loss of Wee1 function will produce smaller than normal daughter cell, because cell division occurs prematurely. (wikipedia.org)
  • The decreased Wee1 activity alone is not sufficient for mitotic entry: Synthesis of cyclins and an activating phosphorylation by a Cdk activating kinase (CAK) are also required. (wikipedia.org)
  • Epigenetic function of Wee1 kinase has also been reported. (wikipedia.org)
  • Although the highly conserved nature of the Cdc25s implies an important role in cell physiology, Cdc25B and Cdc25C knockout mice (both single and double mutants) are viable and display no major alterations in their cell cycles, suggesting some functional compensation either via other Cdk regulatory enzymes (such as Wee1 and Myt1) or from the activity of the third member of the family, Cdc25A. (wikipedia.org)
  • phosphate
  • Kinases should not be confused with phosphorylases, which catalyze the addition of inorganic phosphate groups to an acceptor, nor with phosphatases, which remove phosphate groups. (wikipedia.org)
  • Kinases mediate the transfer of a phosphate moiety from a high energy molecule (such as ATP) to their substrate molecule, as seen in the figure below. (wikipedia.org)
  • Alternatively, some kinases utilize bound metal cofactors in their active sites to coordinate the phosphate groups. (wikipedia.org)
  • bind
  • 2G12 is a broadly neutralizing human monoclonal antibody against individual immunodeficiency pathogen type-1 (HIV-1) which has previously been proven to bind to a carbohydrate-dependent epitope on gp120. (healthandwellnesssource.org)
  • Ligands that bind the Ret receptor include the glial cell line-derived neurotrophic factor (GDNF) and its congeners neurturin, persephin, and artemin (2-4). (cellsignal.com)
  • Cyclins can directly bind the substrate or localize the CDK to a subcellular area where the substrate is found. (wikipedia.org)
  • residue
  • The mitotic cyclins can be grouped as cyclins A & B. These cyclins have a nine residue sequence in the N-terminal region called the "destruction box", which can be recognized by the ubiquitin ligase enzyme which destroys the cyclins when appropriate. (wikipedia.org)