Cyclin-dependent kinase 1

Cyclin-dependent kinase 1
	Existing structural data : 1lc9
Properties of human protein
Mass / length primary structure	297 amino acids
Isoforms	2
Identifier
Gene names	CDC2 ; CDC28
External IDs	OMIM : 116940 ; UniProt : P06493 ;
Enzyme Classifications
EC, category	2.7.11.22 , protein kinase
Response type	Phosphorylation
Substrate	ATP + protein
Products	ADP + phosphoprotein
EC, category	2.7.11.23 , protein kinase
Response type	Phosphorylation
Substrate	ATP + DNA-directed RNA polymerase
Products	ADP + DNA-Directed RNA Polymerase Phosphate
	Orthologue

The cyclin-dependent kinase 1 (CDK1) is the enzyme in the cell nucleus of eukaryotes that initiates the S-phase and thus the next mitotic cell division through phosphorylation of the NuMA protein and the RNA polymerase II . So it is a protein kinase . As part of a protein complex with cyclin B , CDK1 is itself regulated by phosphorylation as a mitosis-promoting factor ; This means that the S-phase process that has been started can be switched off again for a short time. For the initiation of cell division, additional kinases may be necessary in order to release the NuMA protein.

Control of the cell cycle

Various cyclin-CDK complexes initiate the beginning of different steps in the cell cycle. Cyclin-Cdk complexes start the cascade but do not determine how. They have no instructive information and generally have no influence on the cell's growth cycle (see phenotype of the cdc mutants ).

Cyclin-Cdk complexes simultaneously exercise a positive and negative control function. S-Cdk's trigger DNA replication and at the same time prevent the re-replication of already duplicated DNA.

M-Cdk's trigger the start of the M-phase , but at the same time prevent the start of cytokinesis .

Cdk's are like the traffic lights at an intersection, green in one direction and red in the other at the same time.

The discovery of the cdc2 gene

cdc2 was first found in 1987 by Leland H. Hartwell, R. Timothy (Tim) Hunt and Paul M. Nurse in the fission yeast Schizosaccharomyces pombe , who received the 2001 Nobel Prize in Physiology or Medicine for their discoveries on "Controlling the Cell Cycle" .

Leland Hartwell from the Fred Hutchinson Cancer Research Center , Seattle, USA, discovered in the model organism baker's yeast ( Saccharomyces cerevisiae ) a category of genes that code for proteins that control the cell cycle. Among them was a gene, cdc28, the protein of which plays a central role in the beginning of a new cell cycle and was therefore called the “start” by him. In addition, Hartwell introduced the term “ checkpoints ”. The cell cycle is stopped at these points if something goes wrong in the cell cycle phase.

Paul Nurse from the Imperial Cancer Research Fund, London, used genetic and molecular biological methods to identify the protein, namely the cyclin-dependent kinases (CDK). In addition, he was able to show that the defective Cdk gene in yeast can be replaced by the homologous / related gene in humans. This experiment impressively demonstrated the relationship between humans and yeast, one of the simplest eukaryotes.

Tim Hunt of the Imperial Cancer Research Fund, London, discovered cyclins, the proteins that regulate the catalytic activity of CDK. He showed that cyclins are broken down in connection with cell division, a mechanism that has proven to be central to the control of the cell cycle.

The cdc28 gene product of baker's yeast ( Saccharomyces cerevisiae ) as well as the functionally homologous cdc2 gene product in S. Pombe are very similar to the Cdk of humans (CDC2Hs) and the frog.

Cdk complexes form the basis of the cell cycle control system.

Individual evidence

↑ UniProt P06493
↑ Matthews / Merdes / reactome.org: Cyclin B / Cdk1 mediate phosphorylation of NuMA

[1] UniProt P06493

[2] Matthews / Merdes / reactome.org: Cyclin B / Cdk1 mediate phosphorylation of NuMA