CDK2 Human
Description
Introduction to CDK2 Human
Cyclin-dependent kinase 2 (CDK2) is a serine/threonine protein kinase encoded by the CDK2 gene (Entrez Gene ID: 1017) located on chromosome 12q13.2 in humans . It plays a pivotal role in regulating cell cycle progression, particularly transitions from G1 to S phase and S to G2/M phase, by forming complexes with cyclins A and E . CDK2 is ubiquitously expressed, with elevated activity observed in proliferating tissues such as the gastrointestinal tract, lymphoid organs, and testis . Despite being dispensable for embryonic development in mice, CDK2 is critical for meiosis and has emerged as a therapeutic target in oncology due to its dysregulation in cancers .
Core Cell Cycle Regulation
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G1/S Transition: Cyclin E-CDK2 phosphorylates Rb protein, releasing E2F transcription factors to initiate DNA replication .
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S Phase: Cyclin A-CDK2 ensures proper DNA replication and prevents re-replication by phosphorylated pre-replication complex components .
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G2/M Checkpoint: Cooperates with CDK1 to prepare for mitosis .
Non-Cell Cycle Functions
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DNA Repair: Phosphorylates BRCA1, BRCA2, and p53 to coordinate repair with cell cycle progression .
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Transcriptional Regulation: Modulates FOXM1 and SMAD3 activity to link early cell cycle events with mitotic control .
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Apoptosis Resistance: In podocytes, CDK2 suppresses apoptosis by maintaining PDK1-Akt survival signaling .
Cancer Associations
CDK2 overexpression or hyperactivity is linked to:
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Solid Tumors: Breast, ovarian, prostate, and thyroid cancers .
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Hematologic Malignancies: Acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) .
Inhibitors in Clinical Development
Regulatory Mechanisms and Biomarker Potential
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Endogenous Inhibitors: p21Cip1 and p27Kip1 bind CDK2-cyclin complexes to block activity .
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Transcriptional Signature: A 12-gene CDK2 activity score predicts outcomes in gliomas, kidney, and thyroid cancers, outperforming traditional markers like mitotic index .
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Epigenetic Regulation: Microphthalmia-associated transcription factor (MITF) controls CDK2 expression in melanocytes .
Research Challenges and Future Directions
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Compensatory Mechanisms: CDK1 can partially substitute for CDK2 in mitosis, complicating therapeutic targeting .
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Context-Dependent Roles: CDK2 activity correlates with improved survival in colon cancer but predicts poor outcomes in gliomas .
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Combination Therapies: Preclinical synergy between CDK2 inhibitors and PARP inhibitors in BRCA-mutant cancers is under investigation .
Product Specs
Product Science Overview
CDK2 is highly similar to the gene products of Saccharomyces cerevisiae cdc28 and Schizosaccharomyces pombe cdc2, also known as CDK1 in humans . It acts as a catalytic subunit of the cyclin-dependent kinase complex, whose activity is tightly regulated by its association with cyclins, such as cyclin E and cyclin A . Cyclin E binds to CDK2 during the G1 phase, facilitating the transition to the S phase, while cyclin A binds to CDK2 to ensure progression through the S phase .
The activity of CDK2 is regulated by phosphorylation. Inhibitory phosphorylation occurs on threonine 14 and tyrosine 15, while activation requires phosphorylation on threonine 160 . This precise regulation ensures that CDK2 activity is restricted to specific phases of the cell cycle, preventing uncontrolled cell division.
CDK2 is essential for the proper progression of the cell cycle. It has been shown to be indispensable for the G1-S phase transition, although recent studies suggest that cells lacking CDK2 can still progress through the cell cycle, albeit with a lengthened G1 phase . CDK2 is also crucial for meiosis, as its deletion in mice leads to reproductive sterility due to the arrest of germ cells at the prophase of meiosis .
Recombinant human CDK2 is produced using genetic engineering techniques, where the CDK2 gene is cloned and expressed in suitable host cells, such as Escherichia coli or yeast. The recombinant protein is then purified for use in various research applications, including studies on cell cycle regulation, cancer research, and drug development .
CDK2 is a target for cancer research due to its role in cell cycle regulation. Inhibitors of CDK2 are being investigated as potential therapeutic agents for cancer treatment. Additionally, recombinant CDK2 is used in biochemical assays to study its interactions with cyclins and other regulatory proteins, as well as to identify potential substrates and inhibitors .
