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  • 2002
  • Almenara J, Rosato R, Grant S (2002) Synergistic induction of mitochondrial damage and apoptosis in human leukemia cells by flavopiridol and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). (springer.com)
  • Blagosklonny MV, Pardee AB (2002) The restriction point of the cell cycle. (springer.com)
  • CDK6
  • miR-137 has also been shown to directly inhibits CDK6 (Cyclin-dependent kinase 6) expression and decreases the level of phosphorylated RB (retinoblastoma), a known CDK6 downstream target. (wikipedia.org)
  • regulate
  • It can also decrease the expression levels of cytokine receptors, such as the IL-2 receptor to down-regulate the activity of immune cells. (wikipedia.org)
  • Kinases are used extensively to transmit signals and regulate complex processes in cells. (wikipedia.org)
  • PFKFB3's synthesis of F2,6BP in the nucleus was found to regulate Cdk-1, whereas cytosolic PFKFB3 activates PFK-1. (wikipedia.org)
  • interact
  • All four contain an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain that can interact with a multitude of signaling molecules and exhibit both ligand-dependent and ligand-independent activity. (wikipedia.org)
  • At least some cyclins contain a hydrophobic patch which may directly interact with substrates, conferring target specificity. (wikipedia.org)
  • chromosome
  • Two closely connected mechanisms safeguard the fidelity of chromosome segregation in eukaryotic cells. (biochemsoctrans.org)
  • To prevent chromosome missegregation due to early degradation of cyclin B and securin, mitotic checkpoint protein complexes consisting of BubR1, Bub3 and Mad2 bind to and inhibit APC Cdc20 until all chromosomes are properly attached to the mitotic spindle and aligned in the metaphase plate. (biochemsoctrans.org)
  • We found that male fertility and accurate chromosome segregation during spermatogenesis are highly dependent on BubR1, but not Mad2, Bub3, Rae1 and Nup98. (biochemsoctrans.org)
  • Our results suggest that the mechanisms ensuring accurate chromosome segregation differ between mitotic and meiotic cells. (biochemsoctrans.org)
  • Cyclin E-mediated impairment of DNA replication provides a potential mechanism for chromosome instability observed as a consequence of cyclin E deregulation. (rupress.org)
  • Chromosome 10 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the total DNA in cells. (wikipedia.org)
  • cdc2
  • S. pombe and S. cerevisiae are most known for their association with a single Cdk, Cdc2 and Cdc28 respectively, which complexes with several different cyclins. (wikipedia.org)
  • PCNA
  • Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase δ in eukaryotic cells and is essential for replication. (wikipedia.org)
  • PCNA was originally identified as an antigen that is expressed in the nuclei of cells during the DNA synthesis phase of the cell cycle. (wikipedia.org)
  • Antibodies against proliferating cell nuclear antigen (PCNA) or monoclonal antibody termed Ki-67 can be used for grading of different neoplasms, e.g. astrocytoma. (wikipedia.org)
  • Imaging of the nuclear distribution of PCNA (via antibody labeling) can be used to distinguish between early, mid and late S phase of the cell cycle. (wikipedia.org)
  • On the other hand, the study of the dynamics of replication and repair in living cells can be done introducing translational fusions of PCNA. (wikipedia.org)
  • Specifically, p21 has a high affinity for the PIP-box binding region on PCNA, binding of p21 to this region is proposed to block the binding of processivity factors necessary for PCNA dependent S-phase DNA synthesis, but not PCNA dependent nucleotide excision repair (NER). (wikipedia.org)
  • Studies have also demonstrated that the E3 ubiquitin ligase complex CRL4Cdt2 degrades p21 in a PCNA dependent manner over S-phase, necessary to prevent p21 dependent re-replication, as well as in response to UV irradiation. (wikipedia.org)
  • Substrate
  • Substrate specificity of the activated complex is mainly established by the associated cyclin within the complex. (wikipedia.org)
  • Studies have indicated that there is no difference between CDKCs cyclin D1-Cdk4/6, therefore, any unique properties can possibly be linked to substrate specificity or activation. (wikipedia.org)
  • A heat-stable polypeptide present in these extracts, ATP-dependent proteolysis factor 1 (APF-1), was found to become covalently attached to the model protein substrate lysozyme in an ATP- and Mg2+-dependent process. (wikipedia.org)
  • Multiple APF-1 molecules were linked to a single substrate molecule by an isopeptide linkage, and conjugates were found to be rapidly degraded with the release of free APF-1. (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)
  • Kinases properly orient their substrate and the phosphoryl group within their active sites, which increases the rate of the reaction. (wikipedia.org)
  • Kinases are classified into broad groups by the substrate they act upon: protein kinases, lipid kinases, carbohydrate kinases. (wikipedia.org)
  • The cyclins are necessary for the kinase subunit to function with the appropriate substrate. (wikipedia.org)
  • Xenopus
  • Since its initial discovery, homologues of cyclin A have been identified in numerous eukaryotes including Drosophila, Xenopus, mice, and in humans but has not been found in lower eukaryotes like yeast. (wikipedia.org)
  • Cyclin A has been shown to play a crucial role in the G2/M transition in Drosophila and Xenopus embryos. (wikipedia.org)
  • Cln1
  • In S. cerevisiae, the association of Cdc28 with cyclins, Cln1, Cln2, or Cln3, results in the transition from G1 phase to S phase. (wikipedia.org)
  • At the START point in the yeast cell cycle, the G1-cyclins Cln3, Cln1 and Cln 2 activate Cdc28. (wikipedia.org)
  • Sic1 can also be phosphorylated by other kinases, such as Pho85-Pc11 , a kinase which becomes essential when Cln1 and Cln2 are absent. (wikipedia.org)
  • nucleus
  • Cyclin A resides in the nucleus during S phase where it is involved in the initiation and completion of DNA replication. (wikipedia.org)
  • enzyme
  • 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)
  • inhibit
  • Cell cycle arrest may inhibit early cell death of infected cells, allow the cells to evade immune defenses, or help promote virus assembly. (springer.com)
  • In this cell type, p53 activates numerous microRNAs (like miR-302a, miR-302b, miR-302c, and miR-302d) that directly inhibit the p21 expression in hESCs. (wikipedia.org)
  • human
  • This study delineates the antiproliferative activities and in vivo efficacy of YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] in human hepatocellular carcinoma cells. (aspetjournals.org)
  • The metabolite of vitamin D, 1α,25-dihydroxyvitamin D 3 (also known as calcitriol), is a biologically active molecule required to maintain the physiological functions of several target tissues in the human body from conception to adulthood. (mdpi.com)
  • 2014. Genome-wide profiling reveals stimulus-specific functions of p53 during differentiation and DNA damage of human embryonic stem cells. (springer.com)
  • 2013. Lengthened G1 phase indicates differentiation status in human embryonic stem cells. (springer.com)
  • 2010. A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity. (springer.com)
  • Deregulation of cyclin E expression has been associated with a broad spectrum of human malignancies. (rupress.org)
  • However, in terms of signalling outputs and disease relevance, both kinases and pseudokinases are important signalling modulators in human cells, making kinases very important drug targets. (wikipedia.org)
  • This alteration is believed to cause inefficient processing of miR-137 to its mature form, and serve as a mechanism to downregulate miR-137 expression in various human melanoma cell lines. (wikipedia.org)
  • further showed that miR-137 targets Cdc42 (cell division cycle 42), a well-known member of the Rho GTPase family found be upregulated in many human cancer types such as colorectal, testicular and breast cancers. (wikipedia.org)