CDK1

Description

The CDK1 (cyclin dependent kinase 1) is a protein-coding gene located on chromosome 10.

Cyclin-dependent kinase 1, also known as CDK1 or cell division cycle protein 2 homolog, is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in the budding yeast S. cerevisiae, and the fission yeast S. pombe, where it is encoded by genes cdc28 and cdc2, respectively. With its cyclin partners, Cdk1 forms complexes that phosphorylate a variety of target substrates (over 75 have been identified in budding yeast); phosphorylation of these proteins leads to cell cycle progression.

== Structure ==

Cdk1 is a small protein (approximately 34 kilodaltons), and is highly conserved. The human homolog of Cdk1, CDK1, shares approximately 63% amino-acid identity with its yeast homolog. Furthermore, human CDK1 is capable of rescuing fission yeast carrying a cdc2 mutation. Cdk1 is comprised mostly by the bare protein kinase motif, which other protein kinases share. Cdk1, like other kinases, contains a cleft in which ATP fits. Substrates of Cdk1 bind near the mouth of the cleft, and Cdk1 residues catalyze the covalent bonding of the γ-phosphate to the oxygen of the hydroxyl serine/threonine of the substrate. In addition to this catalytic core, Cdk1, like other cyclin-dependent kinases, contains a T-loop, which, in the absence of an interacting cyclin, prevents substrate binding to the Cdk1 active site.

CDK1, also known as CDC2, plays a key role in regulating the eukaryotic cell cycle. It controls the centrosome cycle and the timing of mitosis. CDK1 forms complexes with various cyclins, particularly cyclin B, to drive the G2-M transition. This complex, known as Maturation Promoting Factor (MPF), triggers events like centrosome separation, Golgi dynamics, nuclear envelope breakdown, and chromosome condensation. Once chromosomes align at the metaphase plate, CDK1 activity is deactivated to enable sister chromatid separation and cytokinesis. CDK1 also regulates microtubule dynamics, spindle formation, and various other cellular processes through phosphorylation of a wide range of substrates, including PARVA/actopaxin, APC, AMPH, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, KAT5, LMNA, LMNB, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MLST8, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, TPPP, UL40/R2, RAB4A, RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SAMHD1, SIRT2, CGAS, and RUNX2. CDK1 activity is regulated by phosphorylation, with WEE1 and PKMYT1 inhibiting its activity and CDC25A/B/C activating it. Upon DNA damage, CDK1 is inactivated to allow DNA repair. It is reactivated after successful repair to resume the cell cycle. CDK1 plays a crucial role in early embryonic development and participates in various cellular processes, including apoptosis, cell migration, and gene silencing.

CDK1 is also known as CDC2, CDC28A, P34CDC2.

Associated Diseases

WES Whole Exome Sequencing