CDK1

CDK1 (Cyclin Dependent Kinase 1) is a Protein Coding gene. Diseases associated with CDK1 include Breast Cancer and Retinal Cancer. Among its related pathways are Mitotic Prometaphase and Mitotic Prophase. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is CDK2.

Cyclin Dependent Kinase 1

Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. Required in higher cells for entry into S-phase and mitosis. Phosphorylates PARVA/actopaxin, APC, AMPH, APC, 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, LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, 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 and RUNX2. CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs. Essential for early stages of embryonic development. During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation. Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis. Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair. Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression. In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis. NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis. The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis. In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration. CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis (PubMed:26549230).
Regulates the amplitude of the cyclic expression of the core clock gene ARNTL/BMAL1 by phosphorylating its transcriptional repressor NR1D1, and this phosphorylation is necessary for SCF(FBXW7)-mediated ubiquitination and proteasomal degradation of NR1D1 (PubMed:27238018).
Phosphorylates EML3 at 'Thr-881' which is essential for its interaction with HAUS augmin-like complex and TUBG1 (PubMed:30723163).
(Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry.

Anaphase-promoting complex-dependent catabolic process Source: Reactome
Apoptotic process Source: UniProtKB-KW
Cell division Source: UniProtKB-KW
Cell migration Source: UniProtKB
Centrosome cycle Source: UniProtKB
Ciliary basal body-plasma membrane docking Source: Reactome
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: Reactome
DNA repair Source: UniProtKB
DNA replication Source: UniProtKB
Epithelial cell differentiation Source: UniProtKB
ERK1 and ERK2 cascade Source: Reactome
G2/M transition of mitotic cell cycle Source: GO_Central
Golgi disassembly Source: UniProtKB
Microtubule cytoskeleton organization Source: UniProtKB
Mitotic chromosome condensation Source: Reactome
Mitotic G2 DNA damage checkpoint Source: GO_Central
Mitotic nuclear envelope disassembly Source: Reactome
Mitotic nuclear envelope reassembly Source: Reactome
Negative regulation of apoptotic process Source: UniProtKB
Peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
Peptidyl-threonine phosphorylation Source: ParkinsonsUK-UCL
Positive regulation of G2/M transition of mitotic cell cycle Source: CAFA
Positive regulation of mitochondrial ATP synthesis coupled electron transport Source: CAFA
Positive regulation of protein localization to nucleus Source: UniProtKB
Pronuclear fusion Source: UniProtKB
Protein deubiquitination Source: Reactome
Protein localization to kinetochore Source: BHF-UCL
Protein phosphorylation Source: UniProtKB
Regulation of circadian rhythm Source: UniProtKB
Regulation of embryonic development Source: UniProtKB
Regulation of G2/M transition of mitotic cell cycle Source: Reactome
Regulation of mitotic cell cycle phase transition Source: Reactome
Regulation of Schwann cell differentiation Source: UniProtKB
Regulation of signal transduction by p53 class mediator Source: Reactome
Regulation of transcription initiation from RNA polymerase II promoter Source: Reactome
Rhythmic process Source: UniProtKB-KW

Mitochondrion; Centrosome; Spindle; Nucleus; Cytoplasm. Cytoplasmic during the interphase. Colocalizes with SIRT2 on centrosome during prophase and on splindle fibers during metaphase of the mitotic cell cycle. Reversibly translocated from cytoplasm to nucleus when phosphorylated before G2-M transition when associated with cyclin-B1. Accumulates in mitochondria in G2-arrested cells upon DNA-damage.

Phosphorylation at Thr-161 by CAK/CDK7 activates kinase activity. Phosphorylation at Thr-14 and Tyr-15 by PKMYT1 prevents nuclear translocation. Phosphorylation at Tyr-15 by WEE1 and WEE2 inhibits the protein kinase activity and acts as a negative regulator of entry into mitosis (G2 to M transition). Phosphorylation by PKMYT1 and WEE1 takes place during mitosis to keep CDK1-cyclin-B complexes inactive until the end of G2. By the end of G2, PKMYT1 and WEE1 are inactivated, but CDC25A and CDC25B are activated. Dephosphorylation by active CDC25A and CDC25B at Thr-14 and Tyr-15, leads to CDK1 activation at the G2-M transition. Phosphorylation at Tyr-15 by WEE2 during oogenesis is required to maintain meiotic arrest in oocytes during the germinal vesicle (GV) stage, a long period of quiescence at dictyate prophase I, leading to prevent meiotic reentry. Phosphorylation by WEE2 is also required for metaphase II exit during egg activation to ensure exit from meiosis in oocytes and promote pronuclear formation. Phosphorylated at Tyr-4 by PKR/EIF2AK2 upon genotoxic stress. This phosphorylation triggers CDK1 polyubiquitination and subsequent proteolysis, thus leading to G2 arrest. In response to UV irradiation, phosphorylation at Tyr-15 by PRKCD activates the G2/M DNA damage checkpoint.
Polyubiquitinated upon genotoxic stress.