Cell Cycle Regulation
Representative Targets in Cell Cycle Regulation Full List of Targets in Cell Cycle Regulation Tested Data-Supported Products for Targeting Cell Cycle Regulation
Cell cycle regulation is a fundamental process that orchestrates the sequence of events enabling a cell to divide and replicate accurately, ensuring the maintenance of genomic integrity and proper cellular function. This highly coordinated process is governed by a complex network of signaling pathways, involving a multitude of regulatory proteins, including cyclins, cyclin-dependent kinases (CDKs), and their inhibitors, which together ensure the cell cycle progresses in a controlled manner. The regulation of the cell cycle is pivotal for numerous cellular processes, such as DNA replication, mitosis, and cytokinesis, while also playing a crucial role in tissue growth, development, and the body's response to environmental stimuli and stress. Disruptions in cell cycle regulation can lead to uncontrolled cell proliferation, a hallmark of cancer, underscoring its significance in oncogenesis and the potential for targeted therapeutic interventions. Additionally, cell cycle regulation is integral in the mechanisms of repair and regeneration, where it helps maintain tissue homeostasis and integrity. The precise timing and order of the cell cycle phases—G1, S, G2, and M—are meticulously controlled by the temporal activation and deactivation of CDKs through their association with specific cyclins, alongside the activation of checkpoints that ensure the cell does not proceed to the next phase until it is safe to do so. This intricate balance between cell cycle progression and arrest enables not only the adaptation and survival of cells under varying conditions but also the fine-tuning of developmental and physiological processes, illustrating the complexity and significance of cell cycle regulation in sustaining life.
Figure 1 Cell cycle regulation. (Ding, 2020)
Representative Targets in Cell Cycle Regulation
CCND1
Cyclin D1, encoded by the CCND1 gene, is a pivotal protein that plays a crucial role in regulating cell cycle progression, particularly at the transition from the G1 to the S phase, thereby determining a cell's entry into the DNA synthesis phase. As a regulatory subunit, it partners with cyclin-dependent kinases 4 and 6 (CDK4/6) to phosphorylate the retinoblastoma protein (Rb), leading to the release of E2F transcription factors and the subsequent transcription of genes essential for S phase entry and progression. This mechanism underscores the importance of cyclin D1 in cellular proliferation, differentiation, and development across a wide array of tissues. However, the aberrant expression of cyclin D1, whether through genetic amplification, transcriptional dysregulation, or post-translational modifications, has been implicated in the pathogenesis of several diseases, notably various cancers. Overexpression of cyclin D1 can disrupt normal cell cycle control, promoting uncontrolled cell proliferation and contributing to oncogenesis. It serves not only as a key driver in the development and progression of tumors, including breast, colorectal, and lung cancers, but also as a prognostic marker and a potential therapeutic target. Beyond cancer, alterations in cyclin D1 expression and function have been associated with other pathologies, reflecting its broad impact on cell physiology and disease.
CDK1
CDK1, or Cyclin-Dependent Kinase 1, serves as a fundamental regulator of the eukaryotic cell cycle, orchestrating a wide range of critical cellular processes from cell division to differentiation. As the quintessential member of the cyclin-dependent kinase family, CDK1 forms active complexes with various cyclins, most notably with cyclin B during the G2/M transition, to trigger the onset of mitosis. This activation initiates a cascade of phosphorylation events on a multitude of substrates, leading to the breakdown of the nuclear envelope, chromosome condensation, and the assembly of the mitotic spindle, which are essential for accurate chromosome segregation and cell division. The precise regulation of CDK1 activity is crucial for ensuring the fidelity of the cell cycle; its activity is tightly controlled by mechanisms such as phosphorylation, dephosphorylation, and proteolysis of its cyclin partners. Dysregulation of CDK1 activity, whether through genetic mutations, aberrant expression of its cyclin partners, or failure of its regulatory mechanisms, has been implicated in various pathological conditions, including tumorigenesis, where it can promote uncontrolled cell proliferation. Furthermore, CDK1 plays roles in apoptosis and senescence, acting as a pivotal switch in deciding cell fate under stress conditions. Its central role in cell cycle regulation, coupled with its involvement in disease progression, makes CDK1 a significant target for therapeutic interventions in cancer and other diseases characterized by cell cycle dysregulation.
Recommended Mouse Anti-CDK1 mAb (CAT#: ZG-0397F)
Figure 2 Mouse Anti-CDK1 Recombinant Antibody (ZG-0397F) in ICC. Immunocytochemistry of HeLa cells was performed using anti-CDC2/CDK1 mouse mAb diluted 1:50.
Recommended Mouse Anti-CDK1 mAb (CAT#: ZG-0398F)
Figure 3 Mouse Anti-CDK1 Recombinant Antibody (ZG-0398F) in IHC. Immunohistochemical analysis of paraffin-embedded human lung cancer (A) and esophageal cancer (B) showed cytoplasmic localization by DAB staining with CDC2 monoclonal antibody.
Recommended Mouse Anti-CDK1 mAb (CAT#: ZG-0403F)
Figure 4 Mouse Anti-CDK1 Recombinant Antibody (ZG-0403F) in IF. The Cdk1 monoclonal antibody (green) was used for immunofluorescence analysis of Eca109 cells. Red: Actin filaments have been labeled with Alexa Fluor-555 phalloidin.
CDKN1C
CDKN1C (Cyclin-Dependent Kinase Inhibitor 1C), also known as p57^Kip2, is a key regulator of the cell cycle that plays a critical role in cellular growth, differentiation, and development. As a member of the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors, CDKN1C functions primarily to inhibit the activity of cyclin-CDK2 or cyclin-CDK4 complexes, thereby controlling the cell cycle progression at the G1 phase and preventing the transition from G1 to S phase. This inhibition is crucial for ensuring proper cellular development and function, as it allows cells to exit the cell cycle for differentiation or to enter a quiescent state. Beyond its cell cycle regulatory functions, CDKN1C is involved in several other biological processes, including apoptosis, cellular senescence, and stem cell maintenance, highlighting its versatile role in maintaining cellular homeostasis. Importantly, CDKN1C is subject to tight regulation through genetic and epigenetic mechanisms, and its dysregulation has been implicated in a variety of human diseases. For instance, mutations or alterations in the expression of CDKN1C are associated with a spectrum of developmental disorders and cancers. In particular, loss of function mutations or reduced expression of CDKN1C has been observed in several tumor types, underscoring its potential role as a tumor suppressor gene.
Recommended Mouse Anti-CDKN1C mAb (CAT#: MOB-0160F)
Figure 5 Mouse Anti-CDKN1C Recombinant Antibody (MOB-0160F) in IHC. Immunohistochemical analysis of paraffin-embedded placenta. 1. The antibody is diluted 1:200 (overnight at 4°C). 2. Citric acid, pH 6.0 is used for antigen retrieval. 3. Dilute the secondary antibody at 1:200 (room temperature, 30min).
Recommended Mouse Anti-CDKN1C mAb (CAT#: MOB-0161F)
Figure 6 Mouse Anti-CDKN1C Recombinant Antibody (MOB-0161F) in IHC. Immunohistochemical analysis of paraffin-embedded placenta. 1. The antibody is diluted 1:200 (overnight at 4°C). 2. Use pH 6.0 citrate buffer for antigen retrieval. 3. Dilute the secondary antibody at 1:200 (room temperature, 30min).
Full List of Targets in Cell Cycle Regulation
| Biomarker | Alternative Names | Gene ID | UniProt ID | Roles |
| 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. |
| CCND2 | KIAK0002; MPPH3 | 894 | P30279 | 0 |
| CCND3 | Cyclin D3 | 896 | P30281 | 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. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activtiy is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. Several transcript variants encoding different isoforms have been found for this gene. |
| 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. |
| 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. |
| CDK7 | CAK; CAK1; HCAK; MO15; STK1; CDKN7; P39mo15 | 1022 | P50613 | The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression. This protein forms a trimeric complex with cyclin H and MAT1, which functions as a Cdk-activating kinase (CAK). It is an essential component of the transcription factor TFIIH, that is involved in transcription initiation and DNA repair. This protein is thought to serve as a direct link between the regulation of transcription and the cell cycle. |
| 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. |
| CDKN1C | Cyclin Dependent Kinase Inhibitor 1C; Cyclin-Dependent Kinase Inhibitor 1C (P57, Kip2); Cyclin-Dependent Kinase Inhibitor P57; P57Kip2; KIP2; Cyclin-Dependent Kinase Inhibitor 1C | 1028 | CDKN1C (Cyclin Dependent Kinase Inhibitor 1C) is a Protein Coding gene. Diseases associated with CDKN1C include Beckwith-Wiedemann Syndrome and Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, And Genital Anomalies. Among its related pathways are Primary Focal Segmental Glomerulosclerosis FSGS and DNA Damage. Gene Ontology (GO) annotations related to this gene include cyclin-dependent protein serine/threonine kinase inhibitor activity. An important paralog of this gene is CDKN1B. | |
| 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. |
| CDKN2B | Cyclin Dependent Kinase Inhibitor 2B; Cyclin-Dependent Kinase Inhibitor 2B (P15, Inhibits CDK4); Multiple Tumor Suppressor 2; P14-INK4b; P15-INK4b; P15INK4b; MTS-2; MTS2; Cyclin-Dependent Kinases 4 And 6 Binding Protein; Cyclin-Dependent Kinase 4 Inhibitor B; CDK Inhibitory Protein | 1030 | P42772 | |
| CDKN2C | Cyclin Dependent Kinase Inhibitor 2C; Cyclin-Dependent Kinase Inhibitor 2C (P18, Inhibits CDK4); P18-INK4C; P18-INK6; Cyclin-Dependent Kinase 6 Inhibitor P18; Cyclin-Dependent Kinase 4 Inhibitor C; Cyclin-Dependent Kinase 6 Inhibitor | 1031 | P42773 | CDKN2C (Cyclin Dependent Kinase Inhibitor 2C) is a Protein Coding gene. Diseases associated with CDKN2C include Oligodendroglioma and Choriocarcinoma Of The Testis. Among its related pathways are Cellular Senescence (REACTOME) and Endometrial cancer. Gene Ontology (GO) annotations related to this gene include protein kinase binding and cyclin-dependent protein serine/threonine kinase inhibitor activity. An important paralog of this gene is CDKN2D. |
| MYT1 | MYT1; Human MYT1 | 4661 | Q01538 | |
| NOLC1 | NOLC1; 140 KDa Nucleolar Phosphoprotein; Nucleolar And Coiled-Body Phosphprotein 1; Nucleolar Protein P130; Nucleolar Phosphoprotein P130; NOPP130; HCV NS5A Trans-Regulated Protein 13; KIAA0035; HCV NS5A-Transactivated Protein 13 | 9221 | Q14978 | Related to nucleologenesis, may play a role in the maintenance of the fundamental structure of the fibrillar center and dense fibrillar component in the nucleolus. It has intrinsic GTPase and ATPase activities. May play an important role in transcription catalyzed by RNA polymerase I |
| p53 | 7157 | K7PPA8 | ||
| 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] |
| RBL1 | RB Transcriptional Corepressor Like 1; 107 KDa Retinoblastoma-Associated Protein; Retinoblastoma-Like 1; PRB1; P107; Retinoblastoma-Like Protein 1; CP107 | 5933 | P28749 | The protein encoded by this gene is similar in sequence and possibly function to the product of the retinoblastoma 1 (RB1) gene. The RB1 gene product is a tumor suppressor protein that appears to be involved in cell cycle regulation, as it is phosphorylated in the S to M phase transition and is dephosphorylated in the G1 phase of the cell cycle. Both the RB1 protein and the product of this gene can form a complex with adenovirus E1A protein and SV40 large T-antigen, with the SV40 large T-antigen binding only to the unphosphorylated form of each protein. In addition, both proteins can inhibit the transcription of cell cycle genes containing E2F binding sites in their promoters. Due to the sequence and biochemical similarities with the RB1 protein, it is thought that the protein encoded by this gene may also be a tumor suppressor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008] |
| WEE1 | WEE1; Human WEE1 | 7465 | P30291 |
Tested Data-Supported Products for Targeting Cell Cycle Regulation
Reference
- Ding, Lei, et al. "The roles of cyclin-dependent kinases in cell-cycle progression and therapeutic strategies in human breast cancer." International journal of molecular sciences 21.6 (2020): 1960.
For research use only. Not intended for any clinical use.
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