Chk1 protein. Medical search. Frequent questions

Inhibitor of checkpoint kinase CHK1 was identified as a top screen hit. (nature.com)
Many cancers show aberrant signalling via the insulin-like growth factor (IGF) axis, activating type 1 IGF receptors (IGF-1Rs) and variant insulin receptors (INSRs) to signal via phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) and mitogen-activated protein kinase kinase-extracellular signal-regulated kinases (MEK-ERK) [ 1 ]. (nature.com)
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)
In 1993, Beach and associates initially identified Chk1 as a serine/threonine kinase which regulates the G2/M phase transition in fission yeast. (wikipedia.org)
Chk1 has a N-terminal kinase domain, a linker region, a regulatory SQ/TQ domain and a C-terminal domain. (wikipedia.org)
Two checkpoint kinase subtypes have been identified, Chk1 and Chk2. (wikipedia.org)
In addition, we investigated several cell cycle-related proteins and found that co-knockdown of hTopBP1 and hMYH significantly diminished cell cycle arrest due to compromised checkpoint kinase 1 (Chk1) activation. (biomedcentral.com)
Checkpoint kinase 1 (Chk1, CHEK1) is a Ser/Thr protein kinase that plays a key role in mediating the cellular response to DNA-damage. (rcsb.org)
Most protein kinases share a common ePK (eukaryotic protein kinase) catalytic domain, and can be identified by sequence similarity with Blast or profile hidden Markov models (HMMs). (wormbook.org)
We identified 438 protein kinase genes, including 20 atypical kinases, and an additional 25 kinase fragments or pseudogenes. (wormbook.org)
In the discovery set of fresh-frozen tissue specimens (14), the A-kinase anchor protein 12 (AKAP12) protein was found downregulated across the grades. (nature.com)
Check point kinase 1 (Chk1) is a serine / threonine protein kinase and a key mediator in the DNA damage-induced checkpoint network. (biovendor.com)
Chk1 is an evolutionarily conserved protein kinase that functions to ensure genomic integrity upon genotoxic stress. (biovendor.com)
ChK-1 is a protein kinase that regulates a tumour cell's response to DNA damage often caused by treatment with chemotherapy. (manufacturingchemist.com)
Although intracellular signal transduction is often portrayed as a protein kinase 'domino effect', the counterbalancing function of phosphatases, and thus the control of phosphatase activity, is equally relevant to proper regulation of cellular function. (ac.be)
LY2606368 is a potent and selective ATP competitive inhibitor(IC50=1.5 nM in SW1990 cell) of the Chk1 protein kinase. (chemspider.com)
Proteins involved in the ATM-and-Rad3-related kinase (ATR)-dependent S-phase checkpoint response (Chk1 and Rad17) were also phosphorylated but not ataxia telengectasia mutated kinase. (nih.gov)
Replication blockages activate the ATR kinase which, in turn, activates the downstream effector kinase Chk1 through the mediator protein, Claspin. (caltech.edu)
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)
HEK1 (Checkpoint kinase-1) is also named as CHK1 and belongs to the protein kinase superfamily. (fn-test.com)
Applying "drug target constellation" (DTECT) mapping, we further show that protein levels of TTF1 and cMYC predict response to targeted therapies including aurora kinase, Bcl2, and HSP90 inhibitors. (oncotarget.com)
The presence of replication stress activates the DNA damage response and downstream checkpoint proteins including ataxia telangiectasia and Rad3 related kinase (ATR), checkpoint kinase 1 (CHK1), and WEE1-like protein kinase (WEE1), which trigger cell cycle arrest while protecting and restoring stalled replication forks. (bmj.com)
The protein encoded by this gene belongs to the Ser/Thr protein kinase family. (caslab.com)
Protein kinase D (PKD) enzymes play crucial roles in regulating myocardial contraction, hypertrophy, and remodeling. (bvsalud.org)

4 While proteins can be phosphorylated on nine amino acids, serine, threonine and tyrosine phosphorylation are by far the most predominant in eukaryotic cells. (ac.be)

Chk1 is regulated by ATR through phosphorylation, forming the ATR-Chk1 pathway. (wikipedia.org)
Additional protein interactions are involved to induce maximal phosphorylation of Chk1. (wikipedia.org)
The accumulation of hTopBP1 on chromatin and its subsequent interaction with hRad9 lead to cell cycle arrest, a process mediated by Chk1 phosphorylation and ataxia telangiectasia and Rad3-related protein (ATR) activation. (biomedcentral.com)
To map the mechanisms of aggressiveness we aimed to investigate changes in protein phosphorylation across WHO grades of human meningiomas. (nature.com)
Although viewed as a constitutive housekeeping enzyme in the past, PP2A is a highly regulated phosphatase and is emerging as an important regulator of multiple cellular processes involving protein phosphorylation. (ac.be)
1 Reversible protein phosphorylation is an important regulatory mechanism that controls the activities of a myriad of proteins and is thus involved in virtually every major physiological process. (ac.be)
But advances in the understanding of protein phosphatases make now clear that these enzymes are precisely regulated and are as important as kinases in the regulation of cellular processes involving protein phosphorylation. (ac.be)
Cell cycle progression, phosphorylation, and DNA binding of cell cycle checkpoint proteins were analyzed. (nih.gov)
This protein acts to integrate signals from ATM and ATR, two cell cycle proteins involved in DNA damage responses, that also associate with chromatin in meiotic prophase I. Phosphorylation of CDC25A protein phosphatase by this protein is required for cells to delay cell cycle progression in response to double-strand DNA breaks. (caslab.com)
PKD-dependent site-specific titin phosphorylation in vivo was quantified by mass spectrometry using stable isotope labeling by amino acids in cell culture (SILAC) of SILAC-labeled mouse heart protein lysates that were mixed with lysates isolated from hearts of either wild-type control (WT) or cKO mice. (bvsalud.org)

The demonstrated activity of TZs in this model in combination with a chemotherapeutic agent as well as radiotherapy validates this series of Chk1 inhibitors. (rcsb.org)
Thus, Chk1 inhibitors can preferentially potentiate the efficacy of DNA damaging agents in cancer cells, and Chk1 is an attractive therapeutic target for cancer treatment, especially since approximately 50% of all human cancers are p53-deficient. (biovendor.com)
We also tested PDX tumor response to PARP, CHK1, and ATR inhibitors. (jci.org)
A BRCA2 MUT PDX with high p-CHK1 demonstrated a similar delay of tumor growth in response to PARP, CHK1, and ATR inhibitors. (jci.org)
We find that SCF-cyclin F controls E2F1 ubiquitylation and degradation during the G2/M phase of the cell cycle and upon challenging cells with Chk1 inhibitors. (ox.ac.uk)
Small molecule inhibitors designed to target the DNA damage sensors, such as inhibitors of ataxia telangiectasia-mutated (ATM), ATR, CHK1 and WEE1, impair smooth cell cycle modulation and disrupt efficient DNA repair, or a combination of the above, have demonstrated interesting monotherapy and combinatorial activity, including the potential to reverse drug resistance and have entered developmental pipelines. (bmj.com)

Depletion of CHK1, but not CHK2, induces chromosomal instability and common fragile site breakage. (uri.edu)

Co-inhibition of IGF and CHK1 caused synergistic suppression of cell viability, cell survival and tumour growth in 2D cell culture, 3D spheroid cultures and in vivo. (nature.com)
Investigating the mechanism of synthetic lethality, we reveal that CHK1 inhibition in IGF-1R depleted or inhibited cells further downregulated RRM2, reduced dNTP supply and profoundly delayed replication fork progression. (nature.com)
When the G2 or S checkpoint is abrogated by the inhibition of Chk1, p53- deficient cancer cells undergo mitotic catastrophe and eventually apoptosis, whereas normal cells are still arrested in the G1 phase. (biovendor.com)
Chk1 facilitates the arrest of cell cycle progression and the inhibition of replication origin firing. (caltech.edu)
E2F1 proteolysis via SCF-cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition. (ox.ac.uk)
The screen revealed a striking synthetic lethality between Chk1 inhibition and cyclin F loss. (ox.ac.uk)
Chk1 inhibition in cells lacking cyclin F leads to DNA replication catastrophe. (ox.ac.uk)

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 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)
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)
DNA damage induces the activation of Chk1 which facilitates the initiation of the DNA damage response (DDR) and cell cycle checkpoints. (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)
However, chromatin binding-deficient Claspin proteins can still mediate Chk1 activation in Claspin-depleted extracts, albeit with reduced efficiency. (caltech.edu)
MAD2, standing for mitotic arrest deficient 2, is a spindle checkpoint protein that plays an integral role in the human body. (prospecbio.com)

Activation of ATR phosphorylates a number of downstream proteins that coordinate the cell cycle checkpoint. (biomedcentral.com)
2022 ) CHK1 phosphorylates PRIMPOL to promote replication stress tolerance. (academictree.org)
PKD phosphorylates myofilament proteins, but it is not known whether the giant protein titin is also a PKD substrate. (bvsalud.org)

Isolation and identification of the human homolog of a new p53-binding protein, Mdmx. (univ-amu.fr)

Checkpoint kinases (Chks) are protein kinases that are involved in cell cycle control. (wikipedia.org)
Chk1 activation can also be ATR-independent through interactions with other protein kinases such as PKB/AKT, MAPKAPK and p90/RSK. (wikipedia.org)
Protein kinases are one of the largest and most influential of gene families: constituting some 2% of the proteome, they regulate almost all biochemical pathways and may phosphorylate up to 30% of the proteome. (wormbook.org)
Protein kinases constitute one of the largest and most important of protein families, accounting for ~2% of genes in a variety of eukaryotic genomes. (wormbook.org)
By phosphorylating substrate proteins, kinases modify the activity, location and affinities of up to 30% of all cellular proteins, and direct most cellular processes, particularly in signal transduction and co-ordination of complex pathways. (wormbook.org)
The remaining atypical protein kinases (aPK) belong to several families, some of which have structural, but not sequence similarity to ePKs. (wormbook.org)
In the past, most of the attention was focused primarily on protein kinases and on their regulation, mainly because phosphatases were then viewed as simple housekeeping enzymes. (ac.be)
A synthetic lethality siRNA screen revealed this driving aberration to be selectively targetable in this patient population by inhibiting kinases responsible for stabilisation of the protein such as AURKA and CHK1. (aacrjournals.org)

Recently, Chk1 has shown to mediate DNA repair mechanisms and does so by activating various repair factors. (wikipedia.org)
Claspin has two broadly defined roles, one to mediate Chk1 activation and the other as a component of the replication fork. (caltech.edu)
It is known that replication factors are downregulated during stress and we have observed that cullin 4-based ubiquitin ligase mediate the proteolysis of Mcm10, a protein essential for the initiation and elongation phases of DNA replication. (nii.res.in)
Lossaint G*, Horvat A *, Gire V, Bačević K, Mrouj K, Charrier-Savournin F, Georget V, Fisher D, Dulić V (2022) Reciprocal regulation of p21 and Chk1 controls the cyclin D1-RB pathway to mediate senescence onset after G2 arrest. (irb.hr)

SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence. (cdc.gov)

To overcome the obstacle of radioresistant tumor cells, it is important to identify the critical causes and to develop safe and effective new methods for treatment including the possible use of agents that target ZEB1 and which inhibit CHK1. (mdanderson.org)

The ataxia telangiectasia and Rad3-related protein (ATR) signaling cascade is an important pathway involved in the checkpoint control mechanism [ 3 ]. (biomedcentral.com)

Another focus of this study, DDK, is composed of the catalytic subunit Cdc7 and one of two distinct adaptor proteins, Drf1 or Dbf4. (caltech.edu)

These studies suggest Chk1 depletion can lead to defects in the spindle checkpoint resulting in mitotic abnormalities. (wikipedia.org)
SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. (rupress.org)
Finally, codepletion of Rad51, an important homologous recombination repair protein, abrogates the DNA damage after SET8 depletion. (rupress.org)

Protein Phosphatase 2A (PP2A) is a widely expressed family of protein phosphatases made of a core dimer, composed of a catalytic (C) subunit and a structural (A) subunit, in association with a third variable regulatory (B) subunit. (ac.be)

We identified a replication fork-interacting domain on Claspin that associates with the replication fork proteins and is required for Claspin association with chromatin. (caltech.edu)
Accumulation of Drf1 on chromatin in the presence of replication blocks is dependent upon ATR and Claspin but not Chk1. (caltech.edu)
Each origin is initiated by a combination of regulatory proteins that prepare the chromatin for replication before synthesis (S)-phase entry. (bmj.com)

Chk1 monitors DNA replication in unperturbed cell cycles and responds to genotoxic stress if present. (wikipedia.org)

Exogenous RRM2 expression rescued hallmarks of replication stress induced by co-inhibiting IGF with CHK1 or WEE1, identifying RRM2 as a critical target of the functional IGF:CHK1 and IGF:WEE1 interactions. (nature.com)

Through these findings, it is apparent Chk1 is highly conserved from yeast to humans. (wikipedia.org)

2023 ) Self-reversal facilitates the resolution of HMCES-DNA protein crosslinks in cells. (academictree.org)

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

Outcomes HAMNO is normally selective for DBD-F HAMNO (Fig. 1A) was initially defined as a RPA DBD-F inhibitor within a high-throughput display screen that determined the power of a little molecule to dissociate a Rad9-GST fusion proteins from a RPA-ssDNA complicated, an interaction that will require DBD-F (25). (molecularcircuit.com)

Our results suggested that hMYH is necessary for the accumulation of hTopBP1 to DNA damage lesion to induce the association of hTopBP1 with 9-1-1 and that the interaction between hMYH and hTopBP1 is essential for Chk1 activation. (biomedcentral.com)
There are several interactions that MAD2 shares with others, specifically, binding with Cdc20, in a vital protein-to-protein interaction. (prospecbio.com)
In addition to this interaction, MAD2 also interacts with Chk1, which is integral across multiple points of the cell cycle process, and this is one of the key interactions that plays a massive role in the process. (prospecbio.com)
Functional interaction between the Fanconi anemia D2 protein PCNA via a conserved PCNA-interaction motif. (uri.edu)
The Fanconi Anemia Protein Interaction Network: Casting a Wide Net. (uri.edu)
Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein. (univ-amu.fr)

Chk1 recognizes DNA strand instability during replication and can stall DNA replication in order to allow time for DNA repair mechanisms to restore the genome. (wikipedia.org)
Our laboratory is interested in understanding the mechanisms by which microRNA and checkpoint proteins stall the cell cycle preventing genomic instability and cancer. (nii.res.in)

Chk1 must inactivate in order for the cell to transition from the G2 phase into mitosis, Chk1 expression levels are mediated by regulatory proteins. (wikipedia.org)

Human DNA topoisomerase II-binding protein 1 (hTopBP1) plays an important role in DNA replication and the DNA damage checkpoint pathway. (biomedcentral.com)
Human genome codes for many other single strand DNA binding proteins and we are testing if novel mechanisms of checkpoint activation exist that do not require Replication Protein A. If such mechanisms exist we would like to understand which factors provide the role of DNA binding, how checkpoint proteins like Chk1 and p53 are activated and how signal transduction pathway stalls the cell cycle and DNA replication. (nii.res.in)
The protein products of these genes are thought to act cooperatively in a pathway, the FA-BRCA pathway, to repair DNA damage and prevent cellular transformation. (uri.edu)
A central step in the regulation of the activation of the FA-BRCA pathway is the mono-ubiquitination of the FANCD2 (and FANCI) proteins. (uri.edu)
The ATR/Chk1 pathway is a crucial surveillance network that maintains genomic integrity during DNA replication by stabilizing the replication forks during normal replication in order to avoid replication stress. (molecularcircuit.com)

2 Protein phosphatase 2A (PP2A) is a very abundant - it accounts for as much as 1% of total cellular proteins - ubiquitous and remarkably conserved enzyme. (ac.be)

Regulatory proteins such as replication protein A, Claspin, Tim/Tipin, Rad 17, TopBP1 may be involved to facilitate Chk1 activation. (wikipedia.org)
Mohamed T, Adolph MB, Cortez D. ( 2022 ) Oligomerization of DNA replication regulatory protein RADX is essential to maintain replication fork stability. (academictree.org)

In response to DNA damage, Chk1 is an important signal transducer for G2/M checkpoint activation. (wikipedia.org)

Human DNA topoisomerase II-binding protein 1 (TopBP1) and its orthologs play important roles in DNA replication and checkpoint control [ 1 ]. (biomedcentral.com)

Moreover, we identified a region of Claspin required for association with DDK that lies within the Chk1-binding domain, which contains a series of repeat sequences. (caltech.edu)

Through its interactions with other proteins via its BRCT domains, hTopBP1 performs diverse functions [ 1 ]. (biomedcentral.com)

Here, we show that Claspin associates with several core replication fork proteins in Xenopus egg extracts. (caltech.edu)
Claspin mutant proteins unable to interact with DDK still bind to Chk1 and rescue Chk1 activation in Claspin-depleted extracts. (caltech.edu)

They may sound like words in a children's nursery rhyme, but they are actually the exotic names given to proteins that can generate cells with stem cell-like properties that have the ability to form diverse types of tissue. (mdanderson.org)
One protein with the even more out-there name of ZEB1 (zinc finger E-box binding homeobox 1), is now thought to keep breast cancer cells from being successfully treated with radiation therapy, according to a study at The University of Texas MD Anderson Cancer Center in Houston. (mdanderson.org)
Any obstacles encountered by cells in this process can lead to 'replicative stress' ( Figure 1 ), 1 which may be overcome by replicative stress response proteins, but deficiencies in this response result in accumulated errors in DNA replication and loss of genomic integrity, which lead to cell death. (bmj.com)
They found that in UV-damaged cells, caffeine interrupted the protein ATR-Chk1, which caused the cells to self-destruct, but had no effect on undamaged cells, according to the study published in the Journal of Investigative Dermatology . (dermatologytimes.com)

This is accompanied by DNA double-strand break (DSB) induction and recruitment of the DNA repair proteins replication protein A, Rad51, and 53BP1 to damaged regions. (rupress.org)

Activation of Chk1 holds the cell in the G2 phase until ready to enter the mitotic phase. (wikipedia.org)
Recent breakthroughs have uncovered more and more DNA replication licensing machinery proteins (ORC, Cdc6, Cdt1, geminin, etc.) functioning in other cell cycle events, including centrosome replication, mitotic events, transcription and so on. (intechopen.com)

Chk1 is a central component of genome surveillance pathways and is a key regulator of the cell cycle and cell survival. (wikipedia.org)

This is integral to the whole process, and there is much to think about in the future by way of things like spindle checkpoint signaling, as well as the contribution of other proteins that play a role in the process. (prospecbio.com)

It has been observed that some replication proteins localize to the centrosome suggesting their role in regulation of centrosome biogenesis. (nii.res.in)

Whenever genomic lesions are detected during DNA synthesis, they are coated by the single strand DNA binding protein complex, called Replication Protein A, leading to the activation of canonical checkpoint proteins like ATR, Chk1 and p53. (nii.res.in)

Human Chk1 is located on chromosome 11 on the cytogenic band 11q22-23. (wikipedia.org)
Briefly, miRNAs are expected to account for 1-5% of the human genome and to interfere with at least 30% of the protein-coding genes ( 4 , 5 ). (frontiersin.org)
Cluster analysis of an extensive human breast cancer cell line protein expression map database. (univ-amu.fr)
Horvat A *, Tadijan A*, Vlašić I*, Slade N (2021) p53/p73 Protein Network in Colorectal Cancer and Other Human Malignancies. (irb.hr)

Anatomy20

Organisms6

Diseases10

Chemicals and Drugs129

Analytical, Diagnostic and Therapeutic Techniques and Equipment20

Phenomena and Processes76

Information Science3

Health Care3

Kinase24

Serine1

Phosphorylation10

Inhibitors6

Chk21

Inhibition7

Checkpoints5

Deficient3

Phosphorylates3

Homolog1

Kinases8

Mediate4

Induces DNA Damage1

Inhibit1

Ataxia1

Adaptor Proteins1

Depletion3

Subunit1

Chromatin3

Genotoxic stress1

WEE11

Humans1

Facilitates1

Degradation1

Fusion Proteins1

Interaction6

Instability2

Mitosis1

Pathway5

Phosphatase1

Regulatory2

Checkpoint activation1

TopBP11

Sequences1

Interactions1

Claspin2

Cells4

53BP11

Mitotic2

Cell survival1

Spindle checkpoint1

Regulation1

Single strand1

Human4