Cyclin-Dependent Kinase 2 Associated Protein 1 (CDK2AP1), also known as p12DOC-1 or doc-1 (deleted in oral cancer-1), is a highly conserved and ubiquitously expressed gene located on chromosome 12q24. This gene encodes a 115-amino acid protein that plays a crucial role in regulating the cell cycle and epigenetic mechanisms.
CDK2AP1 is primarily known for its role as a negative regulator of Cyclin-Dependent Kinase 2 (CDK2). It achieves this by sequestering monomeric CDK2 and targeting it for proteolysis . This regulation is essential for maintaining proper cell cycle progression, particularly during the S-phase, where DNA replication occurs .
Additionally, CDK2AP1 interacts with DNA polymerase alpha/primase and mediates the phosphorylation of the large p180 subunit, suggesting a regulatory role in DNA replication . This protein also forms a core subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex, which epigenetically regulates embryonic stem cell differentiation .
CDK2AP1 has been implicated in various malignancies, including oral cancer and prostate cancer . Its downregulation has been observed in several types of cancer, indicating its potential role as a tumor suppressor . In prostate cancer, high CDK2AP1 expression has been associated with worse overall survival and cause-specific survival .
Human recombinant CDK2AP1 is utilized in research to study its role in cell cycle regulation and its potential as a therapeutic target in cancer treatment. By understanding the mechanisms through which CDK2AP1 regulates CDK2 and other cellular processes, researchers aim to develop novel strategies for cancer therapy.