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Cellular pathwaysKinaseProtein DegradationActivatesTumorigenesisApoptosisMitoticSpindleInhibitorsChk1ProgressionGeneGeneticMolecularReplicationIrreversibleCellsControlRoleIncludeIntra-S-phaseDownstreamMitosisKinasesPhosphorylationInhibitYeastPhenotypeTranscriptionUtilizeResponsesInducesGenesCellularMechanismCommonlyRegulatoryMDM2InitiationCell cycleResponsePhaseRepairDriveEventsFeaturesCancer

Cellular pathways1

• Initiation and propagation of tumors reflect underlying genomic alterations such as mutations, polymorphisms, and copy number variations found in genes of multiple cellular pathways. (hindawi.com)

Kinase3

• Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by the CHEK1 gene. (wikipedia.org)
• Two checkpoint kinase subtypes have been identified, Chk1 and Chk2. (wikipedia.org)
• In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. (kegg.jp)

Protein Degradation1

• ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. (kegg.jp)

Activates1

• These ssDNA structures attract ATR and eventually activates the checkpoint pathway. (wikipedia.org)

Tumorigenesis2

• 9 The exact number and nature of genetic alterations and deregulated signalling pathways required for tumorigenesis remains an issue of debate, 10 although it is now clear that central nervous system (CNS) carcinogenesis requires multiple disruptions to the normal cellular circuitry. (bmj.com)
• If cells containing damaged DNA were to divide, the errors would be transmitted to daughter cells, generating genomic instability and resulting in tumorigenesis or apoptosis . (tocris.com)

Apoptosis1

• The DNA damage response is a network of signaling pathways that leads to activation of checkpoints, DNA repair and apoptosis to inhibit damaged cells from progressing through the cell cycle. (wikipedia.org)

Mitotic2

• These studies suggest Chk1 depletion can lead to defects in the spindle checkpoint resulting in mitotic abnormalities. (wikipedia.org)
• These checkpoints may stop the cell cycle after DNA damage, loss of DNA replication or disruption of the mitotic spindle, in order for repair processes to take place. (tocris.com)

Spindle2

• Chk1 has a regulatory role in the spindle checkpoint however the relationship is less clear as compared to checkpoints in other cell cycle stages. (wikipedia.org)
• Studies on Chk1 deficient chicken lymphoma cells have shown increased levels of genomic instability and failure to arrest during the spindle checkpoint phase in mitosis. (wikipedia.org)

Inhibitors2

• In a Phase II study, MD Anderson researchers showed that a regimen of neoadjuvant and adjuvant treatment with checkpoint inhibitors nivolumab, a PD-1 inhibitor, and relatlimab, a LAG-3 inhibitor, was safe and effective in patients with resectable clinical stage III melanoma. (mdanderson.org)
• Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. (kegg.jp)

Chk18

• Chk1 coordinates the DNA damage response (DDR) and cell cycle checkpoint response. (wikipedia.org)
• Activation of Chk1 results in the initiation of cell cycle checkpoints, cell cycle arrest, DNA repair and cell death to prevent damaged cells from progressing through the cell cycle. (wikipedia.org)
• Chk1 is a central component of genome surveillance pathways and is a key regulator of the cell cycle and cell survival. (wikipedia.org)
• Chk1 is required for the initiation of DNA damage checkpoints and has recently been shown to play a role in the normal (unperturbed) cell cycle. (wikipedia.org)
• In addition to mediating cell cycle checkpoints, Chk1 also contributes to DNA repair processes, gene transcription, egg production, embryo development, cellular responses to HIV infection and somatic cell viability. (wikipedia.org)
• In response to DNA damage, Chk1 is an important signal transducer for G2/M checkpoint activation. (wikipedia.org)
• DNA damage induces the activation of Chk1 which facilitates the initiation of the DNA damage response (DDR) and cell cycle checkpoints. (wikipedia.org)
• Chk1 is regulated by ATR through phosphorylation, forming the ATR-Chk1 pathway. (wikipedia.org)

Progression2

• Furthermore, poorer prognosis in cancer patients who display a glycolytic phenotype characterized by metabolic alterations, such as obesity and diabetes, is now well established, providing another link between metabolic pathways and cancer progression. (springer.com)
• Checkpoint control kinases is a term used to describe a group of enzymes that regulate progression of a cell through the cell cycle. (tocris.com)

Gene1

• These alterations can take the form of epigenetic modifications, point mutations, translocations, amplifications or deletions and modify gene functions in ways that deregulate cellular signalling pathways leading to the cancer phenotype. (bmj.com)

Genetic1

• Catastrophic genetic damage can occur if cells progress to the next phase of the cell cycle before the previous phase is properly completed. (tocris.com)

Molecular1

• Intriguingly, many of these mechanisms utilize the same molecular pathways that are altered through calorie and/or carbohydrate restriction. (springer.com)

Replication1

• This pathway recognizes single strand DNA (ssDNA) which can be a result of UV-induced damage, replication stress and inter-strand cross linking. (wikipedia.org)

Irreversible1

• This delay allows time for DNA to repair or cell death to occur if DNA damage is irreversible. (wikipedia.org)

Cells2

• Specifically, the concepts of tumour heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating cells, tumour microenvironment, non-coding sequences and DNA damage response will be reviewed. (bmj.com)
• Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. (kegg.jp)

Control3

• Checkpoint kinases (Chks) are protein kinases that are involved in cell cycle control. (wikipedia.org)
• Checkpoint control kinases function to halt the cell cycle at these critical points. (tocris.com)
• Tocris offers the following scientific literature for Checkpoint Control Kinases to showcase our products. (tocris.com)

Role1

• p53 and its transcriptional targets play an important role in both G1 and G2 checkpoints. (kegg.jp)

Include1

• Intrinsic factors include chronically activated proliferative, invasive, and antiapoptotic signaling pathways. (springer.com)

Intra-S-phase4

• Replication blocks and DNA damage incurred during S phase activate the S-phase and intra-S-phase checkpoint responses, respectively, regulated by the Atrp and Chk1p checkpoint kinases in metazoans. (nih.gov)
• Here we report that Chk1p has a role in the intra-S-phase checkpoint activated when yeast cells replicate their DNA in the presence of low concentrations of hydroxyurea (HU). (nih.gov)
• There are three principal places in the cell cycle at which checkpoints induced by DNA damage function: the border between G1 phase and S phase, intra-S phase, and the border between G2 phase and mitosis ( Fig. 13.3 ). (oncohemakey.com)
• The G1/S and intra-S phase checkpoints inhibit the replication of damaged DNA and work in a coordinated manner with the DNA repair machinery to permit the restitution of DNA integrity, thereby increasing cell survival. (oncohemakey.com)

Downstream3

• Induction of apoptosis via reactivation of p53 (e.g., by inhibitors of HDAC or MDM2) and targeting of its downstream pathways (i.e. (springermedizin.de)
• These Cdk1/Cdc2 regulators are the downstream targets of two well-characterized G2/M checkpoint pathways which prevent cells from entering mitosis when cellular DNA is damaged or when DNA replication is inhibited. (reactome.org)
• Finally, downstream nuclear targets of signaling pathways like the transcription factors Myc and NF-κB, chromatin remodelers, and cell cycle effectors are also commonly altered. (technologynetworks.com)

Mitosis1

• Studies on Chk1 deficient chicken lymphoma cells have shown increased levels of genomic instability and failure to arrest during the spindle checkpoint phase in mitosis. (wikipedia.org)

Kinases1

• Checkpoint kinases (Chks) are protein kinases that are involved in cell cycle control. (wikipedia.org)

Phosphorylation2

• Chk1 is regulated by ATR through phosphorylation, forming the ATR-Chk1 pathway. (wikipedia.org)
• Yeast Chk1p kinase regulates the metaphase-to-anaphase transition in the DNA-damage checkpoint pathway via securin (Pds1p) phosphorylation. (nih.gov)

Inhibit1

• The DNA damage response is a network of signaling pathways that leads to activation of checkpoints, DNA repair and apoptosis to inhibit damaged cells from progressing through the cell cycle. (wikipedia.org)

Yeast2

• However, like Dun1p, yeast Chk1p is not required for the S-phase-checkpoint-induced anaphase block. (nih.gov)
• Checkpoint suppressor 1 suppresses multiple yeast checkpoint mutations including mec1, rad9, rad53 and dun1 by activating a MEC1-independent checkpoint pathway. (nih.gov)

Phenotype1

• Somatic mutations vary in distinct cancer types (eg, brain, pancreas, breast, colon), as well as in a given tumor type, but they do appear to utilize common overlapping oncogenic pathways detected in the malignant phenotype. (medscape.com)

Transcription1

• In addition to mediating cell cycle checkpoints, Chk1 also contributes to DNA repair processes, gene transcription, egg production, embryo development, cellular responses to HIV infection and somatic cell viability. (wikipedia.org)

Utilize1

• The cellular decision as to which pathway to utilize for DSB repair is unclear, however, it appears to be largely influenced by stage within the cell cycle at the time of damage acquisition. (diff.org)

Responses1

• Hyperactivation of these pathways drives tumorigenesis and supports tumor growth.2 Signaling pathway proteins that are commonly activated by physiological responses include growth factor receptor (e.g. (technologynetworks.com)

Induces2

• DNA damage induces the activation of Chk1 which facilitates the initiation of the DNA damage response (DDR) and cell cycle checkpoints. (wikipedia.org)
• Although some aspects of Vpr-induced G2/M arrest resembles induction of host cellular checkpoints, increasing evidence suggests that Vpr induces cell cycle G2 arrest through a mechanism that is to some extent different from the classic G2/M checkpoints. (reactome.org)

Genes3

• [3] Since upregulation of S-phase genes drive further suppression of Whi5 , this pathway creates a positive feedback loop that fully commits cells to S-phase gene expression. (wikipedia.org)
• checkpoint genes ensure that the initiation of late events is delayed until earlier events are complete. (oncohemakey.com)
• Many of the genes commonly mutated encode Purpose and scope INTRODUCTION components or targets of the PI3K/AKT and Ras/ERK pathways, causing dysregulation of cellular signaling.1 This dysregulation drives cancer progression by influencing the behavior of tumor cells through cell proliferation, survival, migration, differentiation, metabolism, polarity, angiogenesis, and the tumor microenvironment. (technologynetworks.com)

Cellular1

• Direct Reversal The simplest of the human DNA repair pathways involves the direct reversal of the highly mutagenic alkylation lesion O6-methylguanine (O6-mG) by the product of the MGMT gene (O6-methylguanine DNA methyltransferase).26 The O6-mG adduct is generated in low levels by the reaction of cellular catabolites with the guanine residues in the DNA. (diff.org)

Mechanism1

• This is the major mechanism of DNA damage induced by charged nuclei (such as a carbon nucleus) and neutrons and is termed high linear energy transfer ( Fig. 13.2 ). (oncohemakey.com)

Commonly2

• Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by the CHEK1 gene. (wikipedia.org)
• This guide highlights some of the key pathways that are commonly dysregulated in cancer. (technologynetworks.com)

Regulatory1

• Chk1 has a regulatory role in the spindle checkpoint however the relationship is less clear as compared to checkpoints in other cell cycle stages. (wikipedia.org)

MDM21

• In response to DNA damage, activated ATM can directly phosphorylate p53 and mdm2, the ubiquitin ligase that targets p53 for degradation. (oncohemakey.com)

Initiation1

• Chk1 is required for the initiation of DNA damage checkpoints and has recently been shown to play a role in the normal (unperturbed) cell cycle. (wikipedia.org)

Cell cycle4

• Chk1 coordinates the DNA damage response (DDR) and cell cycle checkpoint response. (wikipedia.org)
• Chk1 is a central component of genome surveillance pathways and is a key regulator of the cell cycle and cell survival. (wikipedia.org)
• May be involved in DNA damage-inducible cell cycle arrests (checkpoints). (nih.gov)
• Checkpoints are eukaryotic DNA damage-inducible cell cycle arrests at G1 and G2. (nih.gov)

Response2

• In response to DNA damage, Chk1 is an important signal transducer for G2/M checkpoint activation. (wikipedia.org)
• 4 In response to DNA damage, H2AX is rapidly phosphorylated by ATM and localizes to sites of DNA double-strand breaks in multiprotein complexes described as foci ( Fig. 13.4 ). (oncohemakey.com)

Phase2

• In a Phase II study, MD Anderson researchers showed that a regimen of neoadjuvant and adjuvant treatment with checkpoint inhibitors nivolumab, a PD-1 inhibitor, and relatlimab, a LAG-3 inhibitor, was safe and effective in patients with resectable clinical stage III melanoma. (mdanderson.org)
• The G1/S phase checkpoint is the best understood. (oncohemakey.com)

Repair2

• This delay allows time for DNA to repair or cell death to occur if DNA damage is irreversible. (wikipedia.org)
• NER is perhaps the most flexible of the DNA repair pathways considering the diversity of DNA lesions it acts upon. (diff.org)

Drive1

• The 'omics' technology coupled with ultrafast DNA sequencing has led to the identification of dysregulated, overlapping core oncogenic signaling pathways that drive cancer. (medscape.com)

Events1

• This guide highlights a selection of the key events and pathways that are dysregulated and lead to pathogenesis. (technologynetworks.com)

Features1

• The common features of lesions recognized by the NER pathway are that they cause both a helical distortion of the DNA duplex and a modification of the DNA chemistry. (diff.org)

Cancer2

• Effective targeting of aberrant-oncogene addicted and nonaddicted pathways with rational combinations of targeted therapies directed to the hallmarks of cancer will be the key to cure. (medscape.com)
• Benjamin D. Cancer Signaling Pathways and Crosstalk. (technologynetworks.com)