The cell cycle, a fundamental biological process, orchestrates the growth and division of cells through a series of meticulously regulated phases, ensuring genetic material is accurately replicated and distributed to daughter cells. This cycle is under the surveillance of a network of proteins, including cyclins and cyclin-dependent kinases (CDKs), which work in tandem to drive the cell through its cycle phases: G1 (gap 1), S (synthesis), G2 (gap 2), and M (mitosis). Aberrations in this cycle can lead to uncontrolled cell division, a hallmark of cancer. Oncoproteins play a pivotal role in the deregulation of the cancer cell cycle. These proteins, often the result of mutated oncogenes, can disrupt the normal regulatory mechanisms of the cell cycle, leading to uncontrolled cell proliferation, a hallmark of cancer. They act by either directly accelerating cell cycle progression or by inhibiting the function of tumor suppressor proteins, thus evading the cellular checkpoints that usually prevent the progression of cells harboring DNA damage.
Figure 1 Cell cycle checkpoints and their role in cancer cell death. (Chota, 2021)
Cyclin-dependent kinase 4 (CDK4) is a crucial protein enzyme that plays a pivotal role in the regulation of the cell cycle, particularly at the transition from the G1 phase to the S phase, during which the cell prepares for DNA replication. This enzyme, functioning as a serine/threonine kinase, forms a complex with D-type cyclins, and this association is essential for its kinase activity. The CDK4-cyclin D complex phosphorylates the retinoblastoma (Rb) protein, leading to the release of E2F transcription factors that are necessary for the transcription of genes involved in DNA synthesis and cell cycle progression. Thus, CDK4 is instrumental in driving cells through the G1 phase to enter the S phase. Its activity is tightly regulated by specific inhibitors, such as p16INK4a, ensuring the cell cycle proceeds only under appropriate conditions. Dysregulation of CDK4 activity is associated with uncontrolled cell proliferation, making it a significant factor in the development of various cancers.
CCND1, also known as Cyclin D1, is a key regulatory protein that plays a critical role in cell cycle progression, particularly at the G1/S transition. It is a member of the cyclin family, which are characterized by their periodic expression throughout the cell cycle, acting as activators of cyclin-dependent kinases (CDKs). Cyclin D1 forms a complex with CDK4 or CDK6, leading to the phosphorylation of the retinoblastoma protein (Rb), which in turn facilitates the release of E2F transcription factors and initiates the transcription of genes required for S phase entry and DNA replication. Beyond cell cycle control, CCND1 is involved in various cellular processes including apoptosis, differentiation, and metabolism. Its expression is tightly regulated by multiple mechanisms, reflecting its importance in maintaining cellular homeostasis. Dysregulation of Cyclin D1, due to gene amplification, overexpression, or other genetic alterations, is implicated in the pathogenesis of numerous cancers, making it a focal point of research for cancer diagnostics and therapeutics.
Cyclin E, a pivotal component of the cell cycle, is a regulatory protein that plays a crucial role in controlling the transition from the G1 phase to the S phase, thereby enabling DNA replication and cell division. It forms a complex with cyclin-dependent kinase 2 (CDK2), and this interaction is essential for the activation of CDK2, which in turn phosphorylates target proteins to promote cell cycle progression. The levels of cyclin E are tightly regulated through the cell cycle, with its expression peaking at the G1/S transition. This ensures timely progression through the cell cycle and prevents aberrant cell division, which can lead to genomic instability and potentially cancer. Besides its fundamental role in cell cycle regulation, cyclin E has been implicated in various other cellular processes, including apoptosis, DNA repair, and the response to DNA damage. Its overexpression has been observed in a wide range of human cancers, highlighting its importance in maintaining cellular homeostasis and its potential as a therapeutic target.
Biomarker | Alternative Names | Gene ID | UniProt ID | Roles |
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. |
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. |
CAT | Product Name | Biomarker | Assay | Image |
ZG-0404F | Mouse Anti-Cdk4 Recombinant Antibody (ZG-0404F) | Cdk4 | WB | |
ZG-0405F | Mouse Anti-CDK4 Recombinant Antibody (ZG-0405F) | CDK4 | WB | |
ZG-0612J | Rabbit Anti-CDK4 Recombinant Antibody (clone 8F2) | CDK4 | WB | |
ZG-0613J | Rabbit Anti-CDK4 Recombinant Antibody (clone 8H4) | CDK4 | WB | |
VS3-FY346 | Recombinant Rabbit Anti-CDK4 Antibody (clone R04-4I5) | CDK4 | WB | |
VS3-FY347 | Recombinant Rabbit Anti-CDK4 Antibody (clone R04-8I5) | CDK4 | WB | |
VS3-FY348 | Recombinant Rabbit Anti-CDK4 Antibody (clone R07-4G7) | CDK4 | WB |
For research use only. Not intended for any clinical use.
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