Cell Cycle Checkpoint
Representative Targets in Cell Cycle Checkpoint Full List of Targets in Cell Cycle Checkpoint Tested Data-Supported Products for Targeting Cell Cycle Checkpoint
Cell cycle checkpoints are critical regulatory mechanisms that ensure the accuracy and integrity of cell division, serving as surveillance systems that monitor and control the progression of cells through the various phases of the cell cycle. These checkpoints play a pivotal role in maintaining genomic stability by halting cell cycle progression in response to DNA damage, incomplete replication, or other cellular stresses, thus preventing the propagation of damaged or incomplete genetic material to daughter cells. Central to these mechanisms are complexes of proteins that include cyclins, cyclin-dependent kinases (CDKs), and their inhibitors, which work together to regulate the cell cycle's advancement through its distinct phases: G1 (gap 1), S (DNA synthesis), G2 (gap 2), and M (mitosis). The functionality of cell cycle checkpoints is not just limited to the halting of the cell cycle in response to errors; they also orchestrate the repair processes needed to correct detected flaws. For example, in response to DNA damage, the DNA damage checkpoint activates repair mechanisms, and only once the damage has been adequately addressed does the checkpoint allow the cell cycle to proceed. This ensures that cells do not divide with genomic errors that could lead to mutations or chromosomal abnormalities, thereby playing a crucial role in preventing oncogenesis and ensuring tissue homeostasis.
Figure 1 Cell cycle checkpoint pathways impinging upon the cell division cycle. (Chin, 2010)
Representative Targets in Cell Cycle Checkpoint
CDKN1B
CDKN1B, also known as P27KIP1, is a cyclin-dependent kinase (CDK) inhibitor that plays a pivotal role in the regulation of cell cycle progression, specifically acting at the G1 to S phase transition. By binding to and inhibiting the activity of cyclin-CDK complexes, CDKN1B exerts a negative regulatory effect on cell cycle progression, serving as a key checkpoint in controlling cellular proliferation. This function is essential not only for maintaining cellular homeostasis and tissue architecture but also for preventing the unchecked cell growth characteristic of cancer. The importance of CDKN1B extends beyond cell cycle regulation, as it is also involved in cell differentiation, apoptosis, and the response to DNA damage, thereby contributing to the maintenance of genomic integrity and cellular response to stress. Dysregulation of CDKN1B, whether through genetic mutations, altered expression levels, or post-translational modifications, has been implicated in the pathogenesis of a wide range of cancers. Reduced expression or loss of function of CDKN1B promotes cell cycle progression and is associated with increased cell proliferation, tumor growth, and a poor prognosis in cancer patients. Additionally, CDKN1B has been linked to other disease processes, including its role in the regulation of autophagy, senescence, and resistance to chemotherapy.
Recommended Mouse Anti-CDKN1B mAb (CAT#: MOB-0150F)
Figure 2 Mouse Anti-CDKN1B Recombinant Antibody (MOB-0150F) in IHC. Immunohistochemical analysis of paraffin-embedded tonsils. 1. The antibody is diluted 1:200 (overnight at 4°C). 2. Use pH8.0 TRIS-EDTA for antigen retrieval. 3. Dilute the secondary antibody at 1:200 (room temperature, 30min).
Recommended Rabbit Anti-CDKN1B mAb (CAT#: VS3-FY353)
Figure 3 Rabbit Anti-CDKN1B Antibody (ZG-0615J) in IHC. IHC image of ZG-0615J diluted at 1:97.5 and staining in paraffin-embedded human glioma cancer performed on a Leica Bond™ system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4°C overnight. The primary is detected by a biotinylated secondary antibody and visualized using an HRP conjugated SP system.
Recommended Rabbit Anti-CDKN1B mAb (CAT#: VS3-FY354)
Figure 4 Recombinant Rabbit Anti-CDKN1B Antibody (clone R09-6C3) in IHC. Immunohistochemical Analysis of Paraffin-Embedded Human Breast Cancer Using p27 KIP.
RB1
The retinoblastoma protein (RB1) is a fundamental tumor suppressor gene that plays a pivotal role in the regulation of the cell cycle, specifically at the G1/S transition, acting as a guardian of the cell's proliferation checkpoint. RB1 functions by binding to and inhibiting transcription factors of the E2F family, thereby controlling the transcription of genes essential for S phase entry and DNA replication. This interaction is finely regulated by phosphorylation; in its hypophosphorylated state, RB1 is active and capable of inhibiting cell cycle progression, while phosphorylation by cyclin-dependent kinases (CDKs) during the cell cycle leads to its inactivation, allowing for cell cycle progression. The RB1 pathway is critical for preventing uncontrolled cell division, and its disruption can lead to tumorigenesis. RB1 is also involved in processes such as differentiation, apoptosis, and genomic stability, affecting various aspects of cell fate and maintenance of tissue homeostasis. Mutations or functional inactivation of RB1 are implicated in the development of multiple cancers, most notably retinoblastoma, a pediatric eye cancer from which its name is derived. In addition, alterations in the RB1 pathway are observed in breast, lung, and prostate cancers.scence, and resistance to chemotherapy.
Recommended Rabbit Anti-RB1 mAb (CAT#: ZG-0544U)
Figure 5 Rabbit Anti-Phospho-RB1 (S780) Antibody (ZG-0544U) in IP. Immunoprecipitating Phospho-RB1 in Hela whole cell lysate. Lane 1: Rabbit control IgG(1μg) instead of ZG-0544U in Hela whole cell lysate. For western blotting, an HRP-conjugated Protein G antibody was used as the secondary antibody (1/2000). Lane 2: ZG-0544U(3μg) + Hela whole cell lysate(1mg). Lane 3: Hela whole cell lysate (20μg).
SMC1A
SMC1A (Structural Maintenance of Chromosomes 1A) is a core component of the cohesin complex (composed of SMC1A, SMC3, RAD21, and either STAG1 or STAG2), which plays an essential role in chromosome cohesion, DNA repair, and the regulation of gene expression. Cohesin's critical function is to hold sister chromatids together from the time of their replication in S phase until their separation during anaphase, ensuring accurate chromosome segregation and preventing aneuploidy, a common hallmark of cancer. Beyond its canonical role in maintaining genomic stability through chromosome cohesion, SMC1A and the cohesin complex are intricately involved in the repair of DNA double-strand breaks (DSBs) via the homologous recombination (HR) pathway, highlighting its importance in the cellular response to genomic stress and damage. The involvement of SMC1A in regulating gene expression is mediated through its role in organizing the 3D structure of the genome, contributing to the control of transcriptional programs essential for cell differentiation and development. Dysregulation of SMC1A function or expression has been implicated in a range of disease processes, including cancer, where alterations in cohesin components can lead to genomic instability, altered gene expression, and tumor progression. Additionally, mutations in SMC1A are associated with Cornelia de Lange Syndrome (CdLS), a developmental disorder characterized by growth retardation, intellectual disability, and distinct facial features, underscoring the gene's role in developmental processes.
Recommended Mouse Anti-SMC1A mAb (CAT#: ZG-098R)
Figure 6 Mouse Anti-SMC1A Antibody (ZG-098R) in ICC. Immunocytochemistry staining of HeLa cells fixed with 4% Paraformaldehyde and using anti-SMC1A mouse mAb (dilution 1:100)
Recommended Rabbit Anti-SMC1A mAb (CAT#: ZG-0571U)
Figure 7 Rabbit Anti-SMC1A Antibody (ZG-0571U) in IF. IHC image of ZG-0571U diluted at 1:100 and staining in paraffin-embedded human glioma cancer performed on a Leica Bond™ system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4°C overnight. The primary is detected by a Goat anti-rabbit IgG polymer labeled by HRP and visualized using 0.05% DAB.
Full List of Targets in Cell Cycle Checkpoint
| Biomarker | Alternative Names | Gene ID | UniProt ID | Roles |
| ATR | ATR Serine/Threonine Kinase; Ataxia Telangiectasia And Rad3-Related Protein; EC 2.7.11.1; FRP1; MEC1; MEC1, Mitosis Entry Checkpoint 1, Homolog; Ataxia Telangiectasia And Rad3 Related; Mitosis Entry Checkpoint 1; Homolog (S. Cerevisiae); FRAP-Related Protein-1; FRAP-Related Protein 1; FCTCS; SCKL1; SCKL | 545 | Q13535 | The protein encoded by this gene belongs the PI3/PI4-kinase family, and is most closely related to ATM, a protein kinase encoded by the gene mutated in ataxia telangiectasia. This protein and ATM share similarity with Schizosaccharomyces pombe rad3, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. This kinase has been shown to phosphorylate checkpoint kinase CHK1, checkpoint proteins RAD17, and RAD9, as well as tumor suppressor protein BRCA1. Mutations of this gene are associated with Seckel syndrome. An alternatively spliced transcript variant of this gene has been reported, however, its full length nature is not known. Transcript variants utilizing alternative polyA sites exist. |
| ATRIP | ATR Interacting Protein; ATM And Rad3-Related-Interacting Protein; AGS1 | 84126 | Q8WXE1 | This gene encodes an essential component of the DNA damage checkpoint. The encoded protein binds to single-stranded DNA coated with replication protein A. The protein also interacts with the ataxia telangiectasia and Rad3 related protein kinase, resulting in its accumulation at intranuclear foci induced by DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. |
| AURKA | Aurora Kinase A; Protein Phosphatase 1, Regulatory Subunit 47; Serine/Threonine-Protein Kinase Aurora-A; Serine/Threonine-Protein Kinase 6; Breast Tumor-Amplified Kinase; Aurora/IPL1-Related Kinase 1; Aurora 2; STK15; STK6; ARK1; AURA; BTAK; AIK; Serine/Threonine Protein Kinase 15; Serine/Threonine-Protein Kinase 15 | 6790 | O14965 | The protein encoded by this gene is a cell cycle-regulated kinase that appears to be involved in microtubule formation and/or stabilization at the spindle pole during chromosome segregation. The encoded protein is found at the centrosome in interphase cells and at the spindle poles in mitosis. This gene may play a role in tumor development and progression. A processed pseudogene of this gene has been found on chromosome 1, and an unprocessed pseudogene has been found on chromosome 10. Multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008] |
| AURKB | Aurora Kinase B; Protein Phosphatase 1, Regulatory Subunit 48; Serine/Threonine-Protein Kinase Aurora-B; Serine/Threonine-Protein Kinase 12; Serine/Threonine-Protein Kinase 5; Aurora/IPL1-Related Kinase 2; Serine/Threonine Kinase 12; Aurora-Related Kinase 2; EC 2.7.11.1; Aurora-B; Aurora-1; STK12; AIM-1; ARK-2; STK-1; AIK2; AIM1 | 9212 | Q96GD4 | This gene encodes a member of the aurora kinase subfamily of serine/threonine kinases. The genes encoding the other two members of this subfamily are located on chromosomes 19 and 20. These kinases participate in the regulation of alignment and segregation of chromosomes during mitosis and meiosis through association with microtubules. A pseudogene of this gene is located on chromosome 8. Alternatively spliced transcript variants have been found for this gene. |
| BORA | Bora, Aurora Kinase A Activator; C13orf34; Chromosome 13 Open Reading Frame 34; HsBora | 79866 | Q6PGQ7 | BORA is an activator of the protein kinase Aurora A (AURKA; MIM 603072), which is required for centrosome maturation, spindle assembly, and asymmetric protein localization during mitosis. |
| BUB3 | BUB3; Mitotic Checkpoint Protein; BUB3 (Budding Uninhibited By Benzimidazoles 3; Yeast) Homolog; Budding Uninhibited By Benzimidazoles 3 Homolog (Yeast); BUB3 Budding Uninhibited By Benzimidazoles 3 Homolog; Budding Uninhibited By Benzimidazoles 3 Homolog; Mitotic Checkpoint Protein BUB3 | 9184 | O43684 | This gene encodes a protein involved in spindle checkpoint function. The encoded protein contains four WD repeat domains and has sequence similarity with the yeast BUB3 protein. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. |
| CCNA1 | CCNA1; Cyclin A1; Cyclin-A1; CT146 | 8900 | P78396 | The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. The cyclin encoded by this gene was shown to be expressed in testis and brain, as well as in several leukemic cell lines, and is thought to primarily function in the control of the germline meiotic cell cycle. This cyclin binds both CDK2 and CDC2 kinases, which give two distinct kinase activities, one appearing in S phase, the other in G2, and thus regulate separate functions in cell cycle. This cyclin was found to bind to important cell cycle regulators, such as Rb family proteins, transcription factor E2F-1, and the p21 family proteins. Multiple transcript variants encoding different isoforms have been found for this gene. |
| CCNA2 | Cyclin A2; Cyclin-A; CCN1; CCNA; Cyclin-A2; Cyclin A | 890 | P20248 | CCNA2 (Cyclin A2) is a Protein Coding gene. Diseases associated with CCNA2 include Splenic Diffuse Red Pulp Small B-Cell Lymphoma and Valproate Embryopathy. Among its related pathways are CDK-mediated phosphorylation and removal of Cdc6 and Signaling events mediated by PRL. Gene Ontology (GO) annotations related to this gene include protein kinase binding. An important paralog of this gene is CCNA1. |
| CCNB1 | Cyclin B1; CCNB; G2/Mitotic-Specific Cyclin B1; G2/Mitotic-Specific Cyclin-B1; | 891 | P14635 | CCNB1 (Cyclin B1) is a Protein Coding gene. Diseases associated with CCNB1 include Thyroid Lymphoma and Adrenal Carcinoma. Among its related pathways are Mitotic Prometaphase and Mitotic Prophase. Gene Ontology (GO) annotations related to this gene include protein kinase binding and patched binding. An important paralog of this gene is CCNB2. |
| CCNB2 | Cyclin B2; G2/Mitotic-Specific Cyclin-B2; HsT17299 | 9133 | O95067 | CCNB2 (Cyclin B2) is a Protein Coding gene. Diseases associated with CCNB2 include Anauxetic Dysplasia 1 and Breast Cancer. Among its related pathways are Mitotic Prometaphase and Mitotic Prophase. Gene Ontology (GO) annotations related to this gene include protein kinase binding. An important paralog of this gene is CCNB1. |
| CCND1 | Cyclin D1; B-Cell Lymphoma 1 Protein; B-Cell CLL/Lymphoma 1; BCL-1 Oncogene; PRAD1 Oncogene; PRAD1; BCL1; Cyclin D1 (PRAD1: Parathyroid Adenomatosis 1) | 595 | P24385 | G1/S-specific cyclin-D1 (G1/S-specific cyclin D1) is an important protein in cell cycle regulation. It plays a key role in the progression of the G1/S phase of the cell cycle, regulating cell DNA replication and cell division. |
| CDC25A | Cell Division Cycle 25A; EC 3.1.3.48; Dual Specificity Phosphatase CDC25A; Dual Specificity Phosphatase Cdc25A; M-Phase Inducer Phosphatase 1; CDC25 Isoform A1-CAG; CDC25A2-CAG Isoform; CDC25A2 | 993 | P30304 | CDC25A (Cell Division Cycle 25A) is a Protein Coding gene. Diseases associated with CDC25A include Breast Cancer. Among its related pathways are Metabolism of proteins and CDK-mediated phosphorylation and removal of Cdc6. Gene Ontology (GO) annotations related to this gene include protein kinase binding and protein tyrosine phosphatase activity. An important paralog of this gene is CDC25B. |
| CDC25B | Cell division cycle 25B | 994 | P30305 | CDC25B is a member of the CDC25 family of phosphatases. CDC25B activates the cyclin dependent kinase CDC2 by removing two phosphate groups and it is required for entry into mitosis. CDC25B shuttles between the nucleus and the cytoplasm due to nuclear localization and nuclear export signals. The protein is nuclear in the M and G1 phases of the cell cycle and moves to the cytoplasm during S and G2. CDC25B has oncogenic properties, although its role in tumor formation has not been determined. Multiple transcript variants for this gene exist. |
| CDC25C | CDC25; PPP1R60 | 995 | P30307 | This gene encodes a conserved protein that plays a key role in the regulation of cell division. The encoded protein directs dephosphorylation of cyclin B-bound CDC2 and triggers entry into mitosis. It also suppresses p53-induced growth arrest. Multiple alternatively spliced transcript variants of this gene have been described. |
| CDK1 | Cyclin Dependent Kinase 1; Cell Division Cycle 2, G1 To S And G2 To M; Cell Division Control Protein 2 Homolog; Cell Division Protein Kinase 1; P34 Protein Kinase; P34CDC2; CDC28A; | 983 | P06493 | CDK1 (Cyclin Dependent Kinase 1) is a Protein Coding gene. Diseases associated with CDK1 include Breast Cancer and Retinal Cancer. Among its related pathways are Mitotic Prometaphase and Mitotic Prophase. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is CDK2. |
| CDK2 | Cyclin Dependent Kinase 2; Cell Division Protein Kinase 2; P33 Protein Kinase; EC 2.7.11.22; CDKN2; CDC2-Related Protein Kinase; Cyclin-Dependent Kinase 2; P33(CDK2); EC 2.7.11; | 23552 | Q8IZL9 | The protein encoded by this gene belongs to the cdc2/cdkx subfamily of the ser/thr family of protein kinases. |
| CDK4 | CMM3; PSK-J3 | 1019 | P11802 | The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported. |
| CDKN1A | Cyclin Dependent Kinase Inhibitor 1A; Cyclin-Dependent Kinase Inhibitor 1A (P21, Cip1); CDK-Interacting Protein 1; CDKN1; CAP20; MDA-6; CIP1; SDI1; WAF1; P21 | 1026 | A0A024RCX5 | Based on molecular docking results, Ligands-3, 5, 14, and 16 were screened among 17 different Pyrrolone-fused benzosuberene compounds as potent and specific inhibitors without any cross-reactivity against different CDK isoforms. Analysis of MD simulations and MM-PBSA studies, revealed the binding energy profiles of all the selected complexes. |
| CDKN1B | Cyclin Dependent Kinase Inhibitor 1B; Cyclin-Dependent Kinase Inhibitor 1B (P27, Kip1); P27KIP1; KIP1; Cyclin-Dependent Kinase Inhibitor P27; Cyclin-Dependent Kinase Inhibitor 1B; CDKN4; MEN1B; MEN4 | 1027 | P46527 | This protein is encoded by the CDKN1A gene located on chromosome 6 (6p21.2) in humans. |
| CDKN2A | Cyclin Dependent Kinase Inhibitor 2A; Cyclin-Dependent Kinase Inhibitor 2A (Melanoma, P16, Inhibits CDK4); Cyclin-Dependent Kinase 4 Inhibitor A; Cyclin-Dependent Kinase Inhibitor 2A; Multiple Tumor Suppressor 1; Alternative Reading Frame; P16-INK4A; P16INK4A; P14ARF; CDKN2; CDK4I; MTS-1; MTS1; MLM | 1029 | P42771 | CDKN2A loss has been shown to be a significant event in a number of cancer types. While no targeted therapeutic has been engaged in clinical trials, the prognostic impact has been studied by a number of meta-analyses. In majority of cases CDKN2A is inactivated by homozygous deletions. One of the mechanisms by which loss of CDKN2A can occur is by hypermethylation of the promoter region for the gene. |
| CHEK1 | Checkpoint Kinase 1; Cell Cycle Checkpoint Kinase; CHK1 Checkpoint Homolog; EC 2.7.11.1; CHK1; Serine/Threonine-Protein Kinase Chk1; Checkpoint, S. Pombe, Homolog Of, 1 | 1111 | O14757 | The protein encoded by this gene belongs to the Ser/Thr protein kinase family. It is required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. 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. Several alternatively spliced transcript variants have been found for this gene. |
| CHEK2 | Checkpoint Kinase 2; CHK2 Checkpoint Homolog; Cds1 Homolog; HuCds1; RAD53; HCds1; CDS1; CHK2; Serine/Threonine-Protein Kinase Chk2 | 11200 | O96017 | In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene. |
| CYLD | CYLD Lysine 63 Deubiquitinase; Ubiquitin-Specific-Processing Protease CYLD; Cylindromatosis (Turban Tumor Syndrome); Ubiquitin Specific Peptidase Like 2; Deubiquitinating Enzyme CYLD; Ubiquitin Thioesterase CYLD; CYLD1; Probable Ubiquitin Carboxyl-Terminal Hydrolase CYLD; Ubiquitin Carboxyl-Terminal Hydrolase CYLD; Ubiquitin Thiolesterase CYLD; EC 3.4.19.12; EC 3.1.2.15 | 1540 | Q9NQC7 | CYLD (CYLD Lysine 63 Deubiquitinase) is a Protein Coding gene. Diseases associated with CYLD include Cylindromatosis, Familial and Brooke-Spiegler Syndrome. Among its related pathways are Metabolism of proteins and Innate Immune System. Gene Ontology (GO) annotations related to this gene include protein kinase binding and thiol-dependent ubiquitin-specific protease activity. |
| DCTN2 | Dynactin 2 (P50); 50 KDa Dynein-Associated Polypeptide; Dynactin Complex 50 KDa Subunit; P50 Dynamitin; DCTN50; 50 KD Dynein-Associated Polypeptide; Epididymis Secretory Protein Li 77; Dynactin Complex 50 KD Subunit; DYNAMITIN; HEL-S-77; DCTN-50; RBP50 | 10540 | Q13561 | This gene encodes a 50-kD subunit of dynactin, a macromolecular complex consisting of 10-11 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. It is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit is present in 4-5 copies per dynactin molecule. It contains three short alpha-helical coiled-coil domains that may mediate association with self or other dynactin subunits. It may interact directly with the largest subunit (p150) of dynactin and may affix p150 in place. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. |
| E2F1 | E2F1; RBBP3; Transcription factor E2F1; E2F-1; PBR3; Retinoblastoma-associated protein 1; RBAP-1; Retinoblastoma-binding protein 3; RBBP-3; pRB-binding protein E2F-1 | 1869 | Q01094 | The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. |
| E2F2 | E2F-2 | 1870 | Q14209 | The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein and another 2 members, E2F1 and E2F3, have an additional cyclin binding domain. This protein binds specifically to retinoblastoma protein pRB in a cell-cycle dependent manner, and it exhibits overall 46% amino acid identity to E2F1. |
| E2F4 | E2F4 | 1874 | Q16254 | Transcription factor E2F4 is a protein that in humans is encoded by the E2F4 gene. |
| FOXO1 | Forkhead Box O1; Forkhead Box Protein O1A; FOXO1A; FKHR; Forkhead, Drosophila, Homolog Of, In Rhabdomyosarcoma; Forkhead Homolog In Rhabdomyosarcoma; Forkhead In Rhabdomyosarcoma; Forkhead Box Protein O1; FKH1 | 2308 | Q12778 | This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in myogenic growth and differentiation. Translocation of this gene with PAX3 has been associated with alveolar rhabdomyosarcoma. [provided by RefSeq, Jul 2008] |
| FOXO3 | Forkhead Box O3; Forkhead In Rhabdomyosarcoma-Like 1; FKHRL1; FOXO3A; Forkhead, Drosophila, Homolog Of, In Rhabdomyosarcoma-Like 1; Forkhead Homolog (Rhabdomyosarcoma) Like 1; Forkhead Box Protein O3 | 2309 | O43524 | This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. This gene likely functions as a trigger for apoptosis through expression of genes necessary for cell death. Translocation of this gene with the MLL gene is associated with secondary acute leukemia. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008] |
| MAD1L1 | MAD1; PIG9; TP53I9; TXBP181; mitotic spindle assembly checkpoint protein MAD1; MAD1 mitotic arrest deficient like 1; MAD1-like protein 1; mitotic arrest deficient 1-like protein 1; mitotic checkpoint MAD1 protein homolog; mitotic-arrest deficient 1, yeast, homolog-like 1; tax-binding protein 181; tumor protein p53 inducible protein 9 | 8379 | Q9Y6D9 | MAD1L1 is a component of the mitotic spindle-assembly checkpoint that prevents the onset of anaphase until all chromosome are properly aligned at the metaphase plate. MAD1L1 functions as a homodimer and interacts with MAD2L1. MAD1L1 may play a role in cell cycle control and tumor suppression. |
| MAD2L1 | Mitotic Arrest Deficient 2 Like 1; MAD2 (Mitotic Arrest Deficient; Yeast; Homolog)-Like 1; Mitotic Arrest Deficient 2-Like Protein 1; MAD2-Like Protein 1; HSMAD2; MAD2; Mitotic Spindle Assembly Checkpoint Protein MAD2A; Mitotic Arrest Deficient; Yeast; Homolog-Like 1; MAD2 Mitotic Arrest Deficient-Like 1 | 4085 | Q13257 | MAD2L1 is a component of the mitotic spindle assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. MAD2L1 is related to the MAD2L2 gene located on chromosome 1. A MAD2 pseudogene has been mapped to chromosome 14. |
| MDC1 | mediator of DNA damage checkpoint protein1 | 9656 | Q14676 | It reports that MDC1 (mediator of DNA damage checkpoint protein1) regulates many aspects of DNA damage response pathways, such as intra-S phase checkpoint, G2/M checkpoint, and radiation-induced apoptosis. Many proteins, such as ATM, BRCA1, and Chk2, interact with MDC1. MDC1 contains several protein-protein interaction domains. MDC1 appears to function as an adaptor protein, recruiting downstream proteins to upstream kinases and facilitating signal transduction following DNA damage. |
| MRE11 | MRE11 Homolog, Double Strand Break Repair Nuclease; MRE11 Homolog A, Double Strand Break Repair Nuclease; Double-Strand Break Repair Protein MRE11A; Meiotic Recombination 11 Homolog 1; Meiotic Recombination 11 Homolog A; AT-Like Disease; MRE11 Homolog 1; MRE11A; HNGS1; MRE11 Meiotic Recombination 11 Homolog A (S. Cerevisiae); MRE11 Homolog, Double Strand Break Repair Nuclease A | 4361 | P49959 | This gene encodes a nuclear protein involved in homologous recombination, telomere length maintenance, and DNA double-strand break repair. By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 homolog; this complex is required for nonhomologous joining of DNA ends and possesses increased single-stranded DNA endonuclease and 3' to 5' exonuclease activities. In conjunction with a DNA ligase, this protein promotes the joining of noncomplementary ends in vitro using short homologies near the ends of the DNA fragments. This gene has a pseudogene on chromosome 3. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008] |
| NBN | Nibrin; Nijmegen Breakage Syndrome 1 (Nibrin); Cell Cycle Regulatory Protein P95; NBS1; NBS; P95 | 4683 | O60934 | Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008] |
| NEK2 | NLK1; RP67; NEK2A; HsPK21; PPP1R111; serine/threonine-protein kinase Nek2; NIMA (never in mitosis gene a)-related kinase 2 nimA-like protein kinase 1 nimA-related protein kinase 2 protein phosphatase 1, regulatory subunit 111 | 4751 | P51955 | This gene encodes a serine/threonine-protein kinase that is involved in mitotic regulation. This protein is localized to the centrosome, and undetectable during G1 phase, but accumulates progressively throughout the S phase, reaching maximal levels in late G2 phase. Alternatively spliced transcript variants encoding different isoforms with distinct C-termini have been noted for this gene. |
| PLK1 | PLK1; PLK; Serine/threonine-protein kinase PLK1; Polo-like kinase 1; PLK-1; Serine/threonine-protein kinase 13; STPK13 | 5347 | P53350 | The Ser/Thr protein kinase encoded by this gene belongs to the CDC5/Polo subfamily. It is highly expressed during mitosis and elevated levels are found in many different types of cancer. Depletion of this protein in cancer cells dramatically inhibited cell proliferation and induced apoptosis; hence, it is a target for cancer therapy. |
| PLK3 | PLK3; Serine/Threonine-Protein Kinase PLK3; Polo-Like Kinase 3; FGF-Inducible Kinase; FNK; Proliferation-Related Kinase; CNK; Cytokine-Inducible Kinase; EC 2.7.11.21; EC 2.7.11; Cytokine-Inducible Serine/Threonine-Protein Kinase; Polo-Like Kinase 3 (Drosophila); PRK; PLK-3 | 1263 | Q9H4B4 | Cytokine-inducible kinase is a putative serine/threonine kinase. CNK contains both a catalytic domain and a putative regulatory domain. It may play a role in regulation of cell cycle progression and tumorigenesis. |
| RAD50 | RAD50 Double Strand Break Repair Protein; RAD50 Homolog, Double Strand Break Repair Protein; HRad50; RAD50 (S. Cerevisiae) Homolog; RAD50 Homolog (S. Cerevisiae); DNA Repair Protein RAD50; EC 3.6.3.27 | 10111 | Q92878 | The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Rad50, a protein involved in DNA double-strand break repair. This protein forms a complex with MRE11 and NBS1. The protein complex binds to DNA and displays numerous enzymatic activities that are required for nonhomologous joining of DNA ends. This protein, cooperating with its partners, is important for DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. Knockout studies of the mouse homolog suggest this gene is essential for cell growth and viability. Mutations in this gene are the cause of Nijmegen breakage syndrome-like disorder.[provided by RefSeq, Apr 2010] |
| RB1 | RB Transcriptional Corepressor 1; Protein Phosphatase 1, Regulatory Subunit 130; Prepro-Retinoblastoma-Associated Protein; Retinoblastoma 1; P105-Rb; Pp110; PRb; RB | 5925 | P06400 | The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder cancer, and osteogenic sarcoma. [provided by RefSeq, Jul 2008] |
| RPTOR | Regulatory Associated Protein Of MTOR Complex 1; Raptor; P150 Target Of Rapamycin (TOR)-Scaffold Protein Containing WD-Repeats; Regulatory Associated Protein Of MTOR; Complex 1; P150 Target Of Rapamycin (TOR)-Scaffold Protein; Regulatory Associated Protein Of MTOR | 57521 | Q8N122 | This gene encodes a component of a signaling pathway that regulates cell growth in response to nutrient and insulin levels. The encoded protein forms a stoichiometric complex with the mTOR kinase, and also associates with eukaryotic initiation factor 4E-binding protein-1 and ribosomal protein S6 kinase. The protein positively regulates the downstream effector ribosomal protein S6 kinase, and negatively regulates the mTOR kinase. Multiple transcript variants encoding different isoforms have been found for this gene. |
| SMC1A | CDLS2; DEE85; DXS423E; EIEE85; SB1.8; SMC1; SMC1L1; SMC1alpha; SMCB | 8243 | Q14683 | Proper cohesion of sister chromatids is a prerequisite for the correct segregation of chromosomes during cell division. The cohesin multiprotein complex is required for sister chromatid cohesion. This complex is composed partly of two structural maintenance of chromosomes (SMC) proteins, SMC3 and either SMC1L2 or the protein encoded by this gene. Most of the cohesin complexes dissociate from the chromosomes before mitosis, although those complexes at the kinetochore remain. Therefore, the encoded protein is thought to be an important part of functional kinetochores. |
| TFAP2C | ERF1; TFAP2G; hAP-2g; AP2-GAMMA | 7022 | Q92754 | The protein encoded by this gene is a sequence-specific DNA-binding transcription factor involved in the activation of several developmental genes. The encoded protein can act as either a homodimer or heterodimer with other family members and is induced during retinoic acid-mediated differentiation. |
Tested Data-Supported Products for Targeting Cell Cycle Checkpoint
Reference
- Chin, Cheen Fei, and Foong May Yeong. "Safeguarding entry into mitosis: the antephase checkpoint." Molecular and cellular biology 30.1 (2010): 22-32.
For research use only. Not intended for any clinical use.
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