CDK2

GeneName

CDK2

Summary

CDK2, also known as cyclin dependent kinase 2 or CDK-2, is a 34kDa serine/threonine kinase that plays a pivotal role in cell cycle regulation. It forms complexes with cyclins A and E, facilitating the transition between different phases of the cell cycle, particularly the G1/S and G2/M transitions. CDK2 is predominantly expressed in the nucleus and cytoplasm, and it is involved in various processes such as DNA replication, chromatin remodeling, and cellular response to DNA damage. Additionally, it is associated with cellular structures like the centrosome and Cajal bodies, highlighting its importance in cellular organisation and function.

Importance

CDK2 is relevant to: - Cancer research, as its dysregulation can lead to uncontrolled cell proliferation and tumourigenesis - Understanding cell cycle dynamics, which is essential for developing therapies targeting proliferative diseases - Investigating cellular senescence and ageing, given its role in regulating cell division and DNA repair mechanisms - Mechanisms of drug resistance in cancer, as CDK2 activity may influence the efficacy of certain chemotherapeutic agents

Top Products

For researchers investigating CDK2, we highly recommend the top-selling recombinant antibody, Anti-Cdk2 antibody [E304] (ab32147). This well-cited antibody has garnered 283 citations, reflecting its strong reputation in the field. It has been validated in knockout models and is suitable for a variety of applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), immunoprecipitation (IP), and flow cytometry (FC). This versatility makes it an excellent choice for those seeking reliable and consistent results in their CDK2 studies. The Human Cell Cycle In-Cell ELISA Kit (IR) for CDK2 (ab139412) is an excellent option for researchers looking to study CDK2 in the context of the cell cycle.

Abcam Product Citation Summary

The data indicates that CDK2 is frequently studied in the context of cell cycle regulation and proliferation, particularly in human cancer cell lines such as NSCLC and hepatocellular carcinoma. The use of the same antibody across various studies highlights its reliability for detecting CDK2 in different species and cell types, including mouse and rat models.

Abcam Product Citation Table

Function

Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis (PubMed:10499802, PubMed:10884347, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:17495531, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:28216226, PubMed:28666995). Phosphorylates CABLES1, CTNNB1, CDK2AP2, ERCC6, NBN, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, SUV39H1, EZH2 (PubMed:10499802, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:24728993, PubMed:28216226). Triggers duplication of centrosomes and DNA (PubMed:11051553). Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus (PubMed:18372919, PubMed:19238148, PubMed:19561645). Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in embryonic stem cells (ESCs) (PubMed:18372919, PubMed:19238148, PubMed:19561645). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase (PubMed:18372919, PubMed:19238148, PubMed:19561645). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC (PubMed:19966300). Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis (PubMed:15800615, PubMed:20195506, PubMed:21319273). In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation (PubMed:15800615). Involved in regulation of telomere repair by mediating phosphorylation of NBN (PubMed:28216226). Phosphorylation of RB1 disturbs its interaction with E2F1 (PubMed:10499802). NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication (PubMed:11051553). Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase (PubMed:10995386, PubMed:10995387). Required for vitamin D-mediated growth inhibition by being itself inactivated (PubMed:20147522). Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner (PubMed:20079829). USP37 is activated by phosphorylation and thus triggers G1-S transition (PubMed:21596315). CTNNB1 phosphorylation regulates insulin internalization (PubMed:21262353). Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of the C-terminus of protein kinase B (PKB/AKT1 and PKB/AKT2), promoting its activation (PubMed:24670654).

Post-translational modifications

Phosphorylated at Thr-160 by CDK7 in a CAK complex (PubMed:28666995). Phosphorylation at Thr-160 promotes kinase activity, whereas phosphorylation at Tyr-15 by WEE1 reduces slightly kinase activity. Phosphorylated on Thr-14 and Tyr-15 during S and G2 phases before being dephosphorylated by CDC25A.

Nitrosylated after treatment with nitric oxide (DETA-NO).

Sequence Similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Cellular localization

• Cytoplasm
• Cytoskeleton
• Microtubule organizing center
• Centrosome
• Nucleus
• Cajal body
• Cytoplasm
• Endosome
• Localized at the centrosomes in late G2 phase after separation of the centrosomes but before the start of prophase. Nuclear-cytoplasmic trafficking is mediated during the inhibition by 1,25-(OH)(2)D(3).

Alternative names

CDKN2, CDK2, Cyclin-dependent kinase 2, Cell division protein kinase 2, p33 protein kinase

Database links

swissprot:P24941 swissprot:P20248 entrezGene:1017 entrezGene:898 entrezGene:890 swissprot:P24864 omim:123837 omim:123835 omim:116953

Other research areas

• Epigenetics