CDC2; CDK1 (Cyclin-dependent protein kinase 1)

Definition
Cyclin-dependent protein kinase 1 (CDC2/CDK1) is a human gene that encodes the cyclin dependent kinase p34cdk1. It is the catalytic subunit of maturation promoting factor (MPF) which is involved in G2/M phase transition during cell cycle1.

Discovery
Cdc2 was first isolated from purified MPF from Xenopus oocytes by ammonium sulphate precipitation2. It was found that cdc2 could induce germinal vesicle breakdown in the oocytes. Additional experiments in yeast confirmed the protein to be cdc2 product3.

Classification
The protein encoded by cdc2 belongs to a highly conserved family of Ser/Thr protein kinases4.

Structural Characteristics
Cdc2 consists of two lobes, a small N-terminal lobe that binds to cyclin and a large lobe at the C terminus that binds to the substrate4. These lobes are connected by a link between amino acids 80-85. The ATP binding domain is located in the cleft between the two lobes4. Activation of cdc2 requires binding to cyclin and phosphorylation of Thr1614.

Mode of action
Cdc2 plays a major role in the entry of cells into mitosis after DNA replication has been properly completed5. It exists as a heterodimer with cyclin B. During G2 phase of cell cycle, cdc2 is held in an inactive state by phophorylation at Thr14 and Thr15 by wee15. At the end of mitosis, cdc25A protein is activated which in turn dephosphorylates and activates cdc2/cyclinB complex. Activated cdc2/cyclinB complex then stabilizes cdc25A that plays a critical role in transition to mitosis5.

Functions
CyclinB/cdc2 complex is involved in a number of mitotic events both in the nucleus and cytoplasm apart from being important during G1/S phase transition6. It promotes centrosome separation by phosphorylation of centrosome-associated motor protein6. They are involved in nuclear lamina segregation and cell rounding, phosphorylation of APC that is important for sister chromatid separation during anaphase6. Cdc2 also regulates dynamics of spindle tube formation6. Cdc2 has been implicated in various cancers including breast and gastric cancers6. Cdc2 also forms an active complex with cyclin E that and drives cells from G1 to S phase1.

References
1.Kaldis P, Aleem E (2007). Cell cycle sibling rivalry: Cdc2 vs. Cdk2. Cell Cycle, 4 (11), 1491–4.
2.Dunphy WG, Brizuela L, Beach D, and Newport J (1988). The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis. Cell, 54, 423-431.
3.Gautier J, Norbury C, Lohka M, Nurse P and Maller J (1988). Purified maturation-promoting factor contains the product of a Xenopus homolog of the fission yeast cell cycle control gene cdc2+. Cell, 54, 433-439.
4.deBondt HL, Rosenblatt J, Jancarik J, Jones HD, Morgan D0 and Kim SH (1993). Crystal structure of cyclin-dependent kinase 2. Nature, 363, 595-602.
5.Book: Cell Cycle Control edited by Hutchinson C and Glover DM, 121-140.
6.Book: Methods in Molecular Biology, Cell Cycle Control, 296, edited by Humphrey T and Brooks G, 131-138.