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)

Earlier work has shown that there is a periodic change in the rate of production of CO2 during the cell cycle of fission yeast and that this periodicity persists after a block to the DNA-division cycle and also after a block to protein synthesis. It appears that there is a periodic control or 'oscillator' affecting CO2 production that is normally closely entrained to the cell cycle, but which can 'free-run' after a block. In this paper, we examine what events in the DNA-division cycle can generate the entrainment signals and what is the nature of such signals. In the first set of experiments, CO2 production was measured by manometry during induction synchrony produced by blocking the DNA-division cycle in an asynchronous culture for a period and then releasing the block. Synchronous cell division occurs after the release with cell cycles shorter than normal. After release from a block imposed by shifting up the mutant cdc2.33 to the restrictive temperature, oscillations in CO2 production started rapidly and remained closely entrained to the division cycles (with slightly different patterns and timing from those after selection synchrony). This showed that there was an entrainment signal but did not show whether it came from start, the S period or mitosis. A similar experiment with cdc10.129 showed that an early signal came from either start or the S period, as did an experiment with release from N-starvation. The results with cdc25.22 were similar to those with cdc2.33. After a block with hydroxyurea, there was entrainment but with no signs of the early signal that occurred with cdc10. This showed that the early signal came from start and not from the S period. In a second set of double-block experiments, the first block was followed by a second different block. With cdc25.22 followed by MBC (an inhibitor of nuclear division) the cells passed through a narrow window of the cell cycle between the transition point of cdc25.22 and mitosis. This was sufficient to start the oscillations, showing that an entrainment signal could be generated at about the time of mitosis. The results from using hydroxyurea followed by cdc2.33 showed no genuine oscillations, confirming the conclusion from the single hydroxyurea block. The results from using hydroxyurea followed by cdc10.129 confirmed the existence of a mitotic signal.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:CO2 production after induction synchrony of the fission yeast Schizosaccharomyces pombe: the origin and nature of entrainment. 211 27

Introduction: The dysregulation of cell cycle control can lead to cancer development. In breast cancer, cyclin D, CDK 4,6 and the retinoblastoma protein play a central role in the control of cell proliferation, in crosstalk with the estrogen receptor and Her2 pathways. Although the mechanisms by which the CDK4/6 complex is involved in the control of cell growth in triple negative breast cancer (TNBC) are still unclear, some TNBCs might be sensitive to CDK4/6 inhibitors.Areas covered: The authors provide an overview of the treatments that target cell cycle machinery in breast cancer and provide their perspectives for the future.Expert opinion: CDK 4/6 inhibitors are active drugs in HR+ MBC, but some unresolved issues remain. We need to identify biomarkers of response. Moreover, we need to determine the optimal timing for the incorporation of CDK 4/6 inhibitors in the current treatment algorithm. In the Her2 positive subtype, the triple combination of anti Her2 therapies with CDK4/6 inhibitors and endocrine therapy seems to be a promising chemotherapy free approach. Efforts must still be made for the treatment of the TNBC subtype, even though new CDK 4/6 combinations are emerging as promising approaches to selected patients.
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PMID:A clinical evaluation of treatments that target cell cycle machinery in breast cancer. 3161 Jan 39