Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase

  title={Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase},
  author={Li-Huei Tsai and Ed Harlow and Matthew L Meyerson},
CYCLINS are regulatory subunits which associate with kinases to form complexes that control many of the important steps in cell-cycle progression. The best characterized of the cyclin-containing complexes is the association of cyclin B with the p34cdc2 kinase. The p34cdc2/cyclin B complex is required for the G2 to M transition (see refs 1–4 for review), but the physiological role of other cyclin complexes is unclear. Human cyclin A binds independently to two kinases, associating with either… 
Interaction between human cyclin A and adenovirus E1A-associated p107 protein.
The association of p107 with cyclin A suggests a direct link between cell cycle control and the function of p 107, which closely resembles the cell cycle-regulating complexes containing p34cdc2.
The adenovirus E1A-associated kinase consists of cyclin E-p33cdk2 and cyclin A-p33cdk2
The adenovirus E1A oncoproteins form stable complexes with several cellular proteins that include the product of the retinoblastoma gene and a key cell cycle regulatory protein, cyclin A.
Oncogenic activation of cyclin A.
  • C. Bréchot
  • Biology
    Current opinion in genetics & development
  • 1993
Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins.
A two-hybrid protein interaction screen was used to isolate cDNAs encoding human proteins that can interact with human CDK2 in yeast, and a new member of the retinoblastoma susceptibility gene family, Rbr-2 (Rb-related), was obtained, indicating it is the adenovirus E1A-associated p130.
Nuclear localization of vertebrate cyclin A correlates with its ability to form complexes with cdk catalytic subunits.
It is suggested that nuclear transport of cyclin A may depend on the formation of multiprotein complexes comprising cdk catalytic subunits, and the results suggest that A- and B-type cyclins display strikingly distinct subcellular localizations, but the mechanisms underlying these differential distributions are unknown.
Identification of the E2A Gene Products as Regulatory Targets of the G1 Cyclin-dependent Kinases*
  • C. Chu, D. Kohtz
  • Biology, Chemistry
    The Journal of Biological Chemistry
  • 2001
The results suggest that the growth suppressor and transcriptional activator functions of E12/E47 are targets for regulation by G1cyclin-dependent kinases but that the mechanisms of regulation for each function are distinct.
Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation.
The pattern of subunit rearrangement of cyclin-CDK complexes in SV40-transformed cells is also shared in those containing adeno- or papilloma viral oncoproteins, and this findings suggest a mechanism by which oncogenic proteins alter the cell cycle of transformed cells.


Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently from cyclin B
It is reported that human cyclin A messenger RNA and protein levels also vary during the cell cycle, and increase and decrease in advance of cyclin B levels.
A new human p34 protein kinase, CDK2, identified by complementation of a cdc28 mutation in Saccharomyces cerevisiae, is a homolog of Xenopus Eg1.
The results suggest that the machinery controlling the human cell cycle is more complex than that for fission and budding yeast.
Drosophila cdc2 homologs: a functional homolog is coexpressed with a cognate variant.
Results indicate the presence of a closely related cognate of the p34cdc2 cell cycle kinase in Drosophila, which is coexpressed during embryogenesis and that expression is correlated with cell proliferation.
Differential phosphorylation of vertebrate p34cdc2 kinase at the G1/S and G2/M transitions of the cell cycle: identification of major phosphorylation sites.
The results suggest that phosphorylation of Thr 14 and/or Tyr 15 inhibits p34cdc2 kinase activity, in line with the location of these residues within the putative ATP binding site of the kinase.
Mammalian growth-associated H1 histone kinase: a homolog of cdc2+/CDC28 protein kinases controlling mitotic entry in yeast and frog cells.
The data indicate that growth-associated H1 kinase is encoded by a mammalian homolog of cdc2+/CDC28 protein kinase, which controls entry into mitosis in yeast and frog cells.
Control functions of adenovirus transformation region E1A gene products in rat and human cells
It is shown here that neither E3 nor E4 is required, so the effect results directly from an E1A product, which is essential for cell cycle effects; the 243-aa protein is also necessary for the full effect but cannot act alone.
Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product
The interaction between E1A and the retinoblastoma gene product is the first demonstration of a physical link between an oncogene and an anti-oncogene.