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Literature summary for 2.7.11.22 extracted from

  • Liberal, V.; Martinsson-Ahlzen, H.S.; Liberal, J.; Spruck, C.H.; Widschwendter, M.; McGowan, C.H.; Reed, S.I.
    Cyclin-dependent kinase subunit (Cks) 1 or Cks2 overexpression overrides the DNA damage response barrier triggered by activated oncoproteins (2012), Proc. Natl. Acad. Sci. USA, 109, 2754-2759.
    View publication on PubMedView publication on EuropePMC
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Activating Compound

Activating Compound Comment Organism Structure
Cks2 Cks 2 proteins activates Cdk2 Homo sapiens
cyclin E required for activity of Cdk2, cyclin E is an oncoprotein implicated in breast cancer etiology that triggers the DNA damage response Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
co-expression of His-tagged Cdk2/CycE in insect cells Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
Cks1 Cks 1 protein inactivates Cdk2, activation of Chk1 leads to inactivation of Cdk2 by promoting phosphorylation-dependent turnover of the Cdk activating phosphatase Cdc25A Homo sapiens
roscovitine
-
 Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein Cdk2 is inactivated by phosphorylation on Tyr15, Activation of Chk1 leads to inactivation of Cdk2 by promoting phosphorylation-dependent turnover of the Cdkactivating phosphatase Cdc25A. Recombinant His-tagged Cdk2 phosphorylation at Tyr15 by recombinant GST-tagged Wee1 kinase Homo sapiens

Purification (Commentary)

Purification (Comment) Organism
co-purification of recombinant His-tagged Cdk2/CycE from insect cells Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
breast cancer cell
-
 Homo sapiens
-
epithelial cell
-
 Homo sapiens
-
HEK-293 cell
-
 Homo sapiens
-
IME cell
-
 Homo sapiens
-
MCF-7 cell
-
 Homo sapiens
-
MDA-MB-436 cell
-
 Homo sapiens
-
additional information breast cancer-derived cell lines expressed Cks2 mRNA at levels two to fourfold higher than HEK-293A and IME cells Homo sapiens
-
SUM-149PT cell
-
 Homo sapiens
-
ZR75-1 cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + Rb peptide from retinoblastoma-associated protein Homo sapiens ADP + Rb phosphopeptide
-
 ?

Synonyms

Synonyms Comment Organism
CDK2
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Homo sapiens

General Information

General Information Comment Organism
metabolism cyclin-dependent kinase subunit 1 and 2 natural overexpression in human mammary epithelial and breast cancer-derived cells, as well as in other cell types, leads to override of the intra-S-phase checkpoint that blocks DNA replication in response to replication stress. Specifically, binding of Cks1 or Cks2 to cyclin-dependent kinase 2 confers partial resistance to the effects of inhibitory tyrosine phosphorylation mediated by the intra-S-phase checkpoint, allowing cells to continue replicating DNA even under conditions of replicative stress, a mechanism contributing to tumor development. Cks protein overexpression does not affect checkpoint signaling through modulation of Cdk2 inhibitory phosphorylation Homo sapiens
additional information Cks1 subunit is involved in SCF-dependent degradation of Cdk inhibitors, while Cks2 subunit is not. Cks1 deficiency is protective against tumor development in genetically engineered mouse models of lymphoma and mammary tumorigenesis Homo sapiens