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  • residues
  • Without cyclin, a flexible loop called the activation loop or T-loop blocks the cleft, and the position of several key amino acid residues is not optimal for ATP-binding. (wikipedia.org)
  • Cdc25
  • The Cdc25 family appears to have expanded in relation to the complexity of the cell-cycle and life-cycle of higher animals. (wikipedia.org)
  • During the transition of G2 to M phase, cdk1 is de-phosphorylated by CDC25. (wikipedia.org)
  • At the G2/M transition, Cdk1 is activated by Cdc25 through dephosphorylation of Tyr15. (wikipedia.org)
  • degradation
  • Cdk1 phosphorylation also leads to the activation of the ubiquitin-protein ligase APCCdc20, an activation which allows for chromatid segregation and, furthermore, degradation of M-phase cyclins. (wikipedia.org)
  • MPF is disassembled when anaphase-promoting complex (APC) polyubiquitinates cyclin B, marking it for degradation in a negative feedback loop. (wikipedia.org)
  • In intact cells, cyclin degradation begins shortly after the onset of anaphase (late anaphase), the period of mitosis when sister chromatids are separated and pulled toward opposite spindle poles. (wikipedia.org)
  • Different cyclins exhibit distinct expression and degradation patterns that contribute to the temporal coordination of cell cycle events. (wikipedia.org)
  • Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (wikipedia.org)
  • interacts
  • Interacts also with CDK1 (PubMed:16007079). (rcsb.org)
  • p21 interacts with proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. (wikipedia.org)
  • The adenovirus E1A-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E". Genes Dev. (wikipedia.org)
  • Cln3-Cdk1
  • however, when phosphorylated by Cln3-Cdk1, Whi5 is ejected from the nucleus, allowing for transcription of the G1/S regulon, which includes the G1/S cyclins Cln1,2. (wikipedia.org)
  • The pulse of G1/S cyclins causes CLN3-Cdk1 to activate Cln1/2 (start point), as well as Clb5/6 at the initiation of S-phase. (wikipedia.org)
  • CCNB1
  • Re-analyses of mRNA profiling data from primary NB revealed that high level mRNA expression of both cdk1 and its corresponding cyclin, CCNB1, were significantly associated with worse patient outcome independent of MYCN amplification, a strong indicator of adverse NB prognosis. (ugent.be)
  • Cdk1 as well as CCNB1 expression were readily detectable in all embryonal tumor cell lines investigated. (ugent.be)
  • Our results confirm an essential role for the cdk1/CCNB1 complex in tumor cell survival. (ugent.be)
  • checkpoint
  • Recent work has shown that disjunction of sister chromatids, in principle, engages the mitotic checkpoint, and probably also the error correction mechanism, with potentially catastrophic consequences for cell division. (biochemsoctrans.org)
  • Eukaryotic cells have solved this 'anaphase problem' by disabling the mitotic checkpoint at the metaphase-to-anaphase transition. (biochemsoctrans.org)
  • Working in mouse models, it was also shown that whilst mice lacking p21 were healthy, spontaneous tumours developed and G1 checkpoint control was compromised in cells derived from these mice. (wikipedia.org)
  • Besides environmental factors such as nutrients, growth factors and functional load, cell size is also controlled by a cellular cell size checkpoint. (wikipedia.org)
  • Cell size checkpoint: There is evidence for the existence of a cell size checkpoint, which prevents small cells from entering mitosis. (wikipedia.org)
  • In S. pombe this checkpoint delays the mitosis entry of cells with DNA damage (for example induced by gamma radiation). (wikipedia.org)
  • inhibitors
  • See also the PDB gallery below showing interactions with many inhibitors (inc Purvalanol B) In melanocytic cell types, expression of the CDK2 gene is regulated by the Microphthalmia-associated transcription factor. (wikipedia.org)
  • regulatory
  • In the present study, we show a cell-cycle-regulatory role of Mcl-1 involving a shortened form of the Mcl-1 polypeptide, primarily localized to the nucleus, which we call snMcl-1. (biochemj.org)
  • They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved. (wikipedia.org)
  • G1 cyclins do not behave like the other cyclins, in that the concentrations increase gradually (with no oscillation), throughout the cell cycle based on cell growth and the external growth-regulatory signals. (wikipedia.org)
  • Cdr1
  • Nim1/Cdr1 homologue in S. cerevisiae, Hsl1, together with its related kinases Gin4 and Kcc4 localize Swe1 to the bud-neck. (wikipedia.org)
  • tumor
  • Uncontrolled Cdk activity can increase the risk of tumorigenesis, and enhanced Cdk activity occurs in a range of tumor cells. (fredhutch.org)
  • and (5) preferably have activity against tumor cells that are resistant to cisplatin and derivatives. (intechopen.com)
  • Recent preclinical model data additionally show single agent anti-tumor activity in multiple cancer cell lines and tumor xenografts. (clinicaltrials.gov)
  • Inappropriate NHEJ can lead to translocations and telomere fusion, hallmarks of tumor cells. (wikipedia.org)
  • complex
  • Cln1,2 and/or Clb5,6-Cdk1 complex activity leads to a sudden drop in Sic1 levels, allowing for coherent S phase entry. (wikipedia.org)
  • Specifically it contains a Cy1 motif in the N-terminal half, and weaker Cy2 motif in the C-terminal domain that allow it to bind CDK in a region that blocks its ability to complex with cyclins and thus prevent CDK activation. (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)
  • This kinase initiates several complex downstream pathways, which causes a halt in the initiation of new replication origins, prevention of mitosis and replication fork stabilization in order to keep the replication bubble open and DNA polymerase complex attached while the damage is being fixed. (wikipedia.org)
  • The complex Cyclin B/CDK1 a.k.a. (wikipedia.org)
  • only the cyclin-CDK complex is an active kinase. (wikipedia.org)
  • Phosphorylation by CDK-activating kinase (CAK) at Thr 161 on the T-loop increases the complex activity. (wikipedia.org)
  • A cyclin forms a complex with Cdk, which begins to activate the Cdk, but the complete activation requires phosphorylation, as well. (wikipedia.org)
  • The Cdk- G1/S cyclin complex begins to induce the initial processes of DNA replication, primarily by arresting systems that prevent S phase Cdk activity in G1. (wikipedia.org)
  • S cyclins bind to Cdk and the complex directly induces DNA replication. (wikipedia.org)
  • localize
  • Cyclin B1 and B2 can localize Cdk1 to the nucleus and the Golgi, respectively, through a localization sequence outside the CDK-binding region. (wikipedia.org)
  • pathway
  • Since it has been shown that inappropriate activation of Cdk2 is monitored by a p53-dependent pathway, the researchers wondered whether p53 activation in Cdk2AF/AF cells was masking cell cycle defects in Cdk2AF/AF cells. (fredhutch.org)
  • NHEJ is evolutionarily conserved throughout all kingdoms of life and is the predominant double-strand break repair pathway in mammalian cells. (wikipedia.org)
  • The oscillations of the cyclins, namely fluctuations in cyclin gene expression and destruction by the ubiquitin mediated proteasome pathway, induce oscillations in Cdk activity to drive the cell cycle. (wikipedia.org)