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Introduction to Cell Cycle and Its Regulators

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Therapeutic potential of Cell Cycle Kinases in Breast Cancer

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Abstract

The extremely complicated chain of associations among cytokines, proteins, enzymes, and cell cycle signaling pathways orchestrates cell cycle control, which is necessary for cell division, repairing, and development. From a single-celled zygote (fertilized egg), succession of cell divisions creates all multicellular creatures with sexual cycles. As a result, cell proliferation acts as heart for cellular development and growth and it happens at all stages of its life. Cell cycle control primarily governed through the number of CDKs, cyclins, cell cycle signaling pathways, and checkpoints of cell cycle all of which are discussed in this chapter, we will also go over how the cell cycle progresses through different stages. The fundamental regulator of cell cycle advancement is CDKs. The phosphorylation of key substrates by these protein kinases promotes synthesis of DNA and progression of mitosis.

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References

  • Abe K, Watanabe S (1995) Apoptosis of mouse pancreatic acinar cells after duct ligation. Arch Histol Cytol 58(2):221–229

    Article  CAS  PubMed  Google Scholar 

  • Afonso O et al (2014) Feedback control of chromosome separation by a midzone Aurora B gradient. Science 345(6194):332–336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Akhoondi S et al (2007) FBXW7/hCDC4 is a general tumor suppressor in human cancer. Cancer Res 67(19):9006–9012

    Article  CAS  PubMed  Google Scholar 

  • Albert T et al (2014) Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor. Br J Pharmacol 171(1):55–68

    Article  CAS  PubMed  Google Scholar 

  • Angius G et al (2020) Prexasertib, a checkpoint kinase inhibitor: from preclinical data to clinical development. Cancer Chemother Pharmacol 85(1):9–20

    Article  CAS  PubMed  Google Scholar 

  • Asghar U et al (2015) The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat Rev Drug Discov 14(2):130–146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bakkenist CJ, Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421(6922):499–506

    Article  CAS  PubMed  Google Scholar 

  • Blazek D et al (2011) The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes. Genes Dev 25(20):2158–2172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bracken AP et al (2004) E2F target genes: unraveling the biology. Trends Biochem Sci 29(8):409–417

    Article  CAS  PubMed  Google Scholar 

  • Buchkovich KJ, Greider CW (1996) Telomerase regulation during entry into the cell cycle in normal human T cells. Mol Biol Cell 7(9):1443–1454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Canavese M et al (2012) Cyclin dependent kinases in cancer: potential for therapeutic intervention. Cancer Biol Ther 13(7):451–457

    Article  CAS  PubMed  Google Scholar 

  • Cao L et al (2014) Phylogenetic analysis of CDK and cyclin proteins in premetazoan lineages. BMC Evol Biol 14(1):1–16

    Article  Google Scholar 

  • Chen M et al (2011) Loss of the chromatin regulator MRG15 limits neural stem/progenitor cell proliferation via increased expression of the p21 Cdk inhibitor. Stem Cell Res 7(1):75–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choudhuri T et al (2005) Curcumin selectively induces apoptosis in deregulated cyclin D1-expressed cells at G2 phase of cell cycle in a p53-dependent manner. J Biol Chem 280(20):20059–20068

    Article  CAS  PubMed  Google Scholar 

  • Ciardo D et al (2019) On the interplay of the DNA replication program and the intra-S phase checkpoint pathway. Genes 10(2):94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cicenas J, Valius M (2011) The CDK inhibitors in cancer research and therapy. J Cancer Res Clin Oncol 137(10):1409–1418

    Article  CAS  PubMed  Google Scholar 

  • Cimprich KA, Cortez D (2008) ATR: an essential regulator of genome integrity. Rev Mol Cell Biol 9(8):616–627

    Article  CAS  Google Scholar 

  • Clemente-Blanco A et al (2011) Cdc14 phosphatase promotes segregation of telomeres through repression of RNA polymerase II transcription. Nat Cell Biol 13(12):1450–1456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clurman BE et al (1996) Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation. Genes Dev 10(16):1979–1990

    Article  CAS  PubMed  Google Scholar 

  • Courtois G, Gilmore T (2006) Mutations in the NF-κB signaling pathway: implications for human disease. Oncogene 25(51):6831–6843

    Article  CAS  PubMed  Google Scholar 

  • Davis RJ et al (2017) Anti-PD-L1 efficacy can be enhanced by inhibition of myeloid-derived suppressor cells with a selective inhibitor of PI3Kδ/γ. Cancer Res 77(10):2607–2619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DeGregori J et al (1995) Cellular targets for activation by the E2F1 transcription factor include DNA synthesis-and G1/S-regulatory genes. Mol Cell Biol 15(8):4215–4224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deshpande A et al (2005) Cyclins and cdks in development and cancer: a perspective. Oncogene 24(17):2909–2915

    Article  CAS  PubMed  Google Scholar 

  • Dhatchinamoorthy K et al (2018) Regulation of kinetochore configuration during mitosis. Curr Genet 64(6):1197–1203

    Article  CAS  PubMed  Google Scholar 

  • Dulić V et al (1992) Association of human cyclin E with a periodic G1-S phase protein kinase. Science 257(5078):1958–1961

    Article  PubMed  Google Scholar 

  • Elledge SJ (1996) Cell cycle checkpoints: preventing an identity crisis. Science 274(5293):1664–1672

    Article  CAS  PubMed  Google Scholar 

  • Erez N et al (2010) Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-κB-dependent manner. Cancer Cell 17(2):135–147

    Article  CAS  PubMed  Google Scholar 

  • Errico A, Costanzo V (2012) Mechanisms of replication fork protection: a safeguard for genome stability. Crit Rev Biochem Mol Biol 47(3):222–235

    Article  CAS  PubMed  Google Scholar 

  • Evans T et al (1983) Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell 33(2):389–396

    Article  CAS  PubMed  Google Scholar 

  • Fededa JP, Gerlich DW (2012) Molecular control of animal cell cytokinesis. Nat Cell Biol 14(5):440–447

    Article  CAS  PubMed  Google Scholar 

  • Fisher D (2011) Control of DNA replication by cyclin-dependent kinases in development. In: Cell cycle in development. Springer, Berlin, pp 201–217

    Chapter  Google Scholar 

  • Galbraith MD et al (2019) Therapeutic targeting of transcriptional cyclin-dependent kinases. Transcription 10(2):118–136

    Article  CAS  PubMed  Google Scholar 

  • Gavet O, Pines J (2010) Progressive activation of CyclinB1-Cdk1 coordinates entry to mitosis. Dev Cell 18(4):533–543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gerber MR et al (1995) Cdc37 is required for association of the protein kinase Cdc28 with G1 and mitotic cyclins. Proc Natl Acad Sci 92(10):4651–4655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giannone G et al (2019) Role of cyclin-dependent kinase inhibitors in endometrial cancer. Int J Mol Sci 20(9):2353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gibcus JH et al (2018) A pathway for mitotic chromosome formation. Science 359(6376):eaao6135

    Article  PubMed  PubMed Central  Google Scholar 

  • Gieffers C et al (1999) Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons. Proc Natl Acad Sci 96(20):11317–11322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glotzer M et al (1991) Cyclin is degraded by the ubiquitin pathway. Nature 349(6305):132–138

    Article  CAS  PubMed  Google Scholar 

  • Glover L et al (2019) Persistent DNA damage foci and DNA replication with a broken chromosome in the African trypanosome. mBio 10(4):e01252–e01219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Güttinger S et al (2009) Orchestrating nuclear envelope disassembly and reassembly during mitosis. Nat Rev Mol Cell Biol 10(3):178–191

    Article  PubMed  Google Scholar 

  • Haahr P et al (2016) Activation of the ATR kinase by the RPA-binding protein ETAA1. Nat Cell Biol 18(11):1196–1207

    Article  CAS  PubMed  Google Scholar 

  • Hall MC et al (2004) Multi-kinase phosphorylation of the APC/C activator Cdh1 revealed by mass spectrometry. Cell Cycle 3(10):1278–1284

    Article  CAS  PubMed  Google Scholar 

  • Hao B et al (2007) Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases. Mol Cell 26(1):131–143

    Article  CAS  PubMed  Google Scholar 

  • Harbour JW et al (1999) Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell 98(6):859–869

    Article  CAS  PubMed  Google Scholar 

  • Harper JV, Brooks G (2005) The mammalian cell cycle. In: Cell cycle control. Humana Press, New York, pp 113–153

    Google Scholar 

  • Harper JW et al (2002) The anaphase-promoting complex: it’s not just for mitosis any more. Genes Dev 16(17):2179–2206

    Article  CAS  PubMed  Google Scholar 

  • Haupt Y et al (1997) Mdm2 promotes the rapid degradation of p53. Nature 387(6630):296–299

    Article  CAS  PubMed  Google Scholar 

  • Hinds PW et al (1992) Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. Cell 70(6):993–1006

    Article  CAS  PubMed  Google Scholar 

  • Hochegger H et al (2008) Cyclin-dependent kinases and cell-cycle transitions: does one fit all? Nat Rev Mol Cell Biol 9(11):910–916

    Article  CAS  PubMed  Google Scholar 

  • Howell AS, Lew DJ (2012) Morphogenesis and the cell cycle. Genetics 190(1):51–77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang JN et al (2001) Activity of the APCCdh1 form of the anaphase-promoting complex persists until S phase and prevents the premature expression of Cdc20p. J Cell Biol 154(1):85–94

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Irniger S et al (1995) Genes involved in sister chromatid separation are needed for B-type cyclin proteolysis in budding yeast. Cell 81(2):269–277

    Article  CAS  PubMed  Google Scholar 

  • Jaspersen SL et al (1999) Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the kinase Cdc28 and the phosphatase Cdc14. Curr Biol 9(5):227–236

    Article  CAS  PubMed  Google Scholar 

  • Jeronimo C et al (2016) Tail and kinase modules differently regulate core mediator recruitment and function in vivo. Mol Cell 64(3):455–466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeronimo C et al (2015) The histone chaperones FACT and Spt6 restrict H2A. Z from intragenic locations. Mol Cell 58(6):1113–1123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khan T et al (2020) Synergistic activity of agents targeting growth factor receptors, CDKs and downstream signaling molecules in a panel of pancreatic cancer cell lines and the identification of antagonistic combinations: implications for future clinical trials in pancreatic cancer. Oncol Rep 44(6):2581–2594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koepp DM et al (2001) Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science 294(5540):173–177

    Article  CAS  PubMed  Google Scholar 

  • Kolupaeva V, Janssens V (2013) PP1 and PP2A phosphatases–cooperating partners in modulating retinoblastoma protein activation. FEBS J 280(2):627–643

    Article  CAS  PubMed  Google Scholar 

  • Koniaras K et al (2001) Inhibition of Chk1-dependent G2 DNA damage checkpoint radiosensitizes p53 mutant human cells. Oncogene 20(51):7453–7463

    Article  CAS  PubMed  Google Scholar 

  • Lara-Gonzalez P et al (2019) The G2-to-M transition is ensured by a dual mechanism that protects cyclin B from degradation by Cdc20-activated APC/C. Dev Cell 51(3):313–325. e310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lens S, Medema RH (2019) Cytokinesis defects and cancer. Nat Rev Cancer 19(1):32–45

    Article  CAS  PubMed  Google Scholar 

  • Liang P et al (2015) CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell 6(5):363–372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lim S, Kaldis P (2013) Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development 140(15):3079–3093

    Article  CAS  PubMed  Google Scholar 

  • Lim T-G et al (2014) Curcumin suppresses proliferation of colon cancer cells by targeting CDK2 Curcumin inhibits CDK2 to suppress colon cancer cell growth. Cancer Prev Res 7(4):466–474

    Article  CAS  Google Scholar 

  • Limas JC, Cook JG (2019) Preparation for DNA replication: the key to a successful S phase. FEBS Lett 593(20):2853–2867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lisztwan J et al (1998) Association of human CUL-1 and ubiquitin-conjugating enzyme CDC34 with the F-box protein p45SKP2: evidence for evolutionary conservation in the subunit composition of the CDC34–SCF pathway. EMBO J 17(2):368–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lockhead S et al (2020) The apparent requirement for protein synthesis during G2 phase is due to checkpoint activation. Cell Rep 32(2):107901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Magnussen GI et al (2012) High expression of Wee1 is associated with poor disease-free survival in malignant melanoma: potential for targeted therapy. PLoS One 7(6):e38254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malumbres M (2014) Cyclin-dependent kinases. Genome Biol 15(6):1–10

    Article  Google Scholar 

  • Malumbres M, Barbacid M (2001) To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer 1(3):222–231

    Article  CAS  PubMed  Google Scholar 

  • Mao J-H et al (2004) Fbxw7/Cdc4 is a p53-dependent, haplo insufficient tumour suppressor gene. Nature 432(7018):775–779

    Article  CAS  PubMed  Google Scholar 

  • Marqués-Torrejón MÁ et al (2013) Cyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression. Cell Stem Cell 12(1):88–100

    Article  PubMed  Google Scholar 

  • Martín A et al (2005) Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27Kip1 and p21Cip1. Cancer Cell 7(6):591–598

    Article  PubMed  Google Scholar 

  • Masaki T et al (2003) Cyclins and cyclin-dependent kinases: comparative study of hepatocellular carcinoma versus cirrhosis. Hepatology 37(3):534–543

    Article  CAS  PubMed  Google Scholar 

  • Maskey D et al (2015) Cell cycle-dependent ubiquitylation and destruction of NDE 1 by CDK 5-FBW 7 regulates ciliary length. EMBO J 34(19):2424–2440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuoka M et al (1998) Interferon-α-induced G1 phase arrest through up-regulated expression of CDK inhibitors, p19Ink4D and p21Cip1 in mouse macrophages. Oncogene 16(16):2075–2086

    Article  CAS  PubMed  Google Scholar 

  • Mehraj U et al (2022a) Expression pattern and prognostic significance of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) in breast cancer: a comprehensive analysis. Adv Cancer Biol Metastasis 4:100037

    Article  CAS  Google Scholar 

  • Mehraj U et al (2021a) Tumor microenvironment promotes breast cancer chemoresistance. Cancer Chemother Pharmacol 87:147–158

    Article  PubMed  Google Scholar 

  • Mehraj U et al (2021b) Prognostic significance and targeting tumor-associated macrophages in cancer: new insights and future perspectives. Breast Cancer 28(3):539–555

    Article  PubMed  Google Scholar 

  • Mehraj U et al (2022b) Expression pattern and prognostic significance of CDKs in breast cancer: an integrated bioinformatic study. Cancer Biomark 34:505–519

    Article  CAS  PubMed  Google Scholar 

  • Mierzwa B, Gerlich DW (2014) Cytokinetic abscission: molecular mechanisms and temporal control. Dev Cell 31(5):525–538

    Article  CAS  PubMed  Google Scholar 

  • Mir MA et al (2020) Targeting different pathways using novel combination therapy in triple negative breast cancer. Curr Cancer Drug Targets 20(8):586–602

    Article  CAS  PubMed  Google Scholar 

  • Mitri Z et al (2015) A phase 1 study with dose expansion of the CDK inhibitor dinaciclib (SCH 727965) in combination with epirubicin in patients with metastatic triple negative breast cancer. Investig New Drugs 33(4):890–894

    Article  CAS  Google Scholar 

  • Moseley JB et al (2009) A spatial gradient coordinates cell size and mitotic entry in fission yeast. Nature 459(7248):857–860

    Article  CAS  PubMed  Google Scholar 

  • Nelson DM et al (2002) Coupling of DNA synthesis and histone synthesis in S phase independent of cyclin/cdk2 activity. Mol Cell Biol 22(21):7459–7472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohtsubo M et al (1995) Human cyclin E, a nuclear protein essential for the G1-to-S phase transition. Mol Cell Biol 15(5):2612–2624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orlando DA et al (2008) Global control of cell-cycle transcription by coupled CDK and network oscillators. Nature 453(7197):944–947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ortega S et al (2002) Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim Biophy Acta 1602(1):73–87

    CAS  Google Scholar 

  • Paulson JR, Laemmli U (1977) The structure of histone-depleted metaphase chromosomes. Cell 12(3):817–828

    Article  CAS  PubMed  Google Scholar 

  • Peters J-M (2002) The anaphase-promoting complex: proteolysis in mitosis and beyond. Mol Cell 9(5):931–943

    Article  CAS  PubMed  Google Scholar 

  • Pines J, Hunter T (1991) Cyclin-dependent kinases: a new cell cycle motif? Trends Cell Biol 1(5):117–121

    Article  CAS  PubMed  Google Scholar 

  • Pippa R et al (2012) p27Kip1 represses transcription by direct interaction with p130/E2F4 at the promoters of target genes. Oncogene 31(38):4207–4220

    Article  CAS  PubMed  Google Scholar 

  • Qayoom H et al (2022) Expression patterns and therapeutic implications of CDK4 across multiple carcinomas: a molecular docking and MD simulation study. Med Oncol 39(10):1–13

    Article  Google Scholar 

  • Qiao R et al (2016) Mechanism of APC/CCDC20 activation by mitotic phosphorylation. Proc Natl Acad Sci 113(19):E2570–E2578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rane SG et al (2002) Germ line transmission of the Cdk4 R24C mutation facilitates tumorigenesis and escape from cellular senescence. Mol Cell Biol 22(2):644–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren S, Rollins BJ (2004) Cyclin C/cdk3 promotes Rb-dependent G0 exit. Cell 117(2):239–251

    Article  CAS  PubMed  Google Scholar 

  • Riabowol K et al (1989) The cdc2 kinase is a nuclear protein that is essential for mitosis in mammalian cells. Cell 57(3):393–401

    Article  CAS  PubMed  Google Scholar 

  • Ronco C et al (2017) ATM, ATR, CHK1, CHK2 and WEE1 inhibitors in cancer and cancer stem cells. Medchemcomm 8(2):295–319

    Article  CAS  PubMed  Google Scholar 

  • Roos WP, Kaina B (2006) DNA damage-induced cell death by apoptosis. Trends Mol Med 12(9):440–450

    Article  CAS  PubMed  Google Scholar 

  • Saldivar JC et al (2018) An intrinsic S/G2 checkpoint enforced by ATR. Science 361(6404):806–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Samejima K et al (2012) Mitotic chromosomes are compacted laterally by KIF4 and condensin and axially by topoisomerase IIα. J Cell Biol 199(5):755–770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santaguida S, Musacchio A (2009) The life and miracles of kinetochores. EMBO J 28(17):2511–2531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santo L et al (2015) Targeting cyclin-dependent kinases and cell cycle progression in human cancers. Semin Oncol 42:788

    Article  CAS  PubMed  Google Scholar 

  • Schiel JA et al (2012) FIP3-endosome-dependent formation of the secondary ingression mediates ESCRT-III recruitment during cytokinesis. Nat Cell Biol 14(10):1068–1078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seif F et al (2017) The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal 15(1):1–13

    Article  Google Scholar 

  • Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13(12):1501–1512

    Article  CAS  PubMed  Google Scholar 

  • Shuai K, Liu B (2003) Regulation of JAK–STAT signalling in the immune system. Nat Rev Immunol 3(11):900–911

    Article  CAS  PubMed  Google Scholar 

  • Siu KT et al (2012) An integrated view of cyclin E function and regulation. Cell Cycle 11(1):57–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sofi S et al (2022a) Targeting cyclin-dependent kinase 1 (CDK1) in cancer: molecular docking and dynamic simulations of potential CDK1 inhibitors. Med Oncol 39(9):1–15

    Article  Google Scholar 

  • Sofi S et al (2022b) Cyclin-dependent kinases in breast cancer: expression pattern and therapeutic implications. Med Oncol 39(6):1–16

    Article  Google Scholar 

  • Sotillo R et al (2001) Wide spectrum of tumors in knock-in mice carrying a Cdk4 protein insensitive to INK4 inhibitors. EMBO J 20(23):6637–6647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Srinivas US et al (2019) ROS and the DNA damage response in cancer. Redox Biol 25:101084

    Article  CAS  PubMed  Google Scholar 

  • Su K-C et al (2016) A regulatory switch alters chromosome motions at the metaphase-to-anaphase transition. Cell Rep 17(7):1728–1738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sullivan M, Morgan DO (2007) Finishing mitosis, one step at a time. Nat Rev Mol Cell Biol 8(11):894–903

    Article  CAS  PubMed  Google Scholar 

  • Taylor-Harding B et al (2015) Cyclin E1 and RTK/RAS signaling drive CDK inhibitor resistance via activation of E2F and ETS. Oncotarget 6(2):696

    Article  PubMed  Google Scholar 

  • Thu K et al (2018) Targeting the cell cycle in breast cancer: towards the next phase. Cell Cycle 17(15):1871–1885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toteja R (2008) Cell cycle and cell cycle regulation. National Institute of Science Communication and Information Resources (NISCAIR), New Delhi

    Google Scholar 

  • van den Heuvel S, Harlow E (1993) Distinct roles for cyclin-dependent kinases in cell cycle control. Science 262(5142):2050–2054

    Article  PubMed  Google Scholar 

  • Vassilev LT et al (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303(5659):844–848

    Article  CAS  PubMed  Google Scholar 

  • Vavrdová T et al (2019) Phosphorylation of plant microtubule-associated proteins during cell division. Front Plant Sci 10:238

    Article  PubMed  PubMed Central  Google Scholar 

  • Vermeulen K et al (2003) The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif 36(3):131–149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Viladevall L et al (2009) TFIIH and P-TEFb coordinate transcription with capping enzyme recruitment at specific genes in fission yeast. Mol Cell 33(6):738–751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Visconti R et al (2016) Cell cycle checkpoint in cancer: a therapeutically targetable double-edged sword. J Exp Clin Cancer Res 35(1):1–8

    Article  Google Scholar 

  • Welcker M et al (2003) Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. Mol Cell 12(2):381–392

    Article  CAS  PubMed  Google Scholar 

  • Whittaker SR et al (2018) Molecular profiling and combinatorial activity of CCT 068127: a potent CDK 2 and CDK 9 inhibitor. Mol Oncol 12(3):287–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whittaker SR et al (2017) Inhibitors of cyclin-dependent kinases as cancer therapeutics. Pharmacol Ther 173:83–105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wohlbold L et al (2012) Chemical genetics reveals a specific requirement for Cdk2 activity in the DNA damage response and identifies Nbs1 as a Cdk2 substrate in human cells. PLoS Genet 8(8):e1002935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wordeman L (2010) How kinesin motor proteins drive mitotic spindle function: lessons from molecular assays. Semin Cell Dev Biol 21:260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yavuz M, et al (2021) Condition medium of glioblastoma cell lines decreases the viability of glioblastoma cells by modulating gene expression profile. bioRxiv. https://doi.org/10.1101/2021.09.11.459916

  • Ying H et al (2020) TRIM59 promotes tumor growth in hepatocellular carcinoma and regulates the cell cycle by degradation of protein phosphatase 1B. Cancer Lett 473:13–24

    Article  CAS  PubMed  Google Scholar 

  • Yu S-Y et al (2014) Induction of p21Waf1/Cip1 by garcinol via downregulation of p38-MAPK signaling in p53-independent H1299 lung cancer. J Agric Food Chem 62(9):2085–2095

    Article  CAS  PubMed  Google Scholar 

  • Zhang J et al (2019) Targeting cyclin-dependent kinases in gastrointestinal cancer therapy. Discov Med 27(146):27–36

    PubMed  Google Scholar 

  • Zhao J et al (2001) Transcriptional activation of cyclin D1 promoter by FAK contributes to cell cycle progression. Mol Biol Cell 12(12):4066–4077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng XD et al (2007) Phosphorylation of Rga2, a Cdc42 GAP, by CDK/Hgc1 is crucial for Candida albicans hyphal growth. EMBO J 26(16):3760–3769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Bioresources, School of Biological Sciences, University of Kashmir, Srinagar, J&K, India

    Manzoor Ahmad Mir & Asma Jan

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    Manzoor Mir

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Mir, M.A., Jan, A. (2023). Introduction to Cell Cycle and Its Regulators. In: Mir, M. (eds) Therapeutic potential of Cell Cycle Kinases in Breast Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-19-8911-7_3

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