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FLASH GENE
Symbol CDK1 contributors: mct/ - updated : 27-12-2021
HGNC name cyclin-dependent kinase 1
HGNC id 1722
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveesophagus   highly
 salivary gland   highly
Endocrineadrenal gland   highly
Lymphoid/Immunelymph node   predominantly
Reproductivefemale systemuterus  moderately
 female systembreastmammary gland highly
Urinarybladder   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow   
Connectivebone   
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
cell cycle     cell cycle, checkpoint, G1S, G2M
Text umbilical cord and embryonic tissue
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • serine/threonine kinase p34/cdc2 with the PSTAIRE motif
  • an ATP binding site
    • HOMOLOGY
    interspecies ortholog to Cdk1, Rattus norvegicus
    ortholog to CDK1, Mus musculus
    ortholog to cdk&, Danio rerio
    ortholog to CDK1, Pan troglodytes
    Homologene
    FAMILY
  • protein kinase superfamily
  • CMGC Ser/Thr protein kinase family
  • CDC2/CDKX subfamily
    • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleoplasm
    text continually shuttling between the nucleus and cytoplasm
    basic FUNCTION
  • directly regulates microtubule dynamics at mitosis through phosphorylation of MAP4 (
  • cdc2-mediated phosphorylation is an important regulator of nestin organization and dynamics during mitosis (
  • acting as an histone 1-kinase (H1K)
  • involved in cell cycle regulation (G1 to S and G2 to M transition)
  • phosphorylating JUNB and lowering its level in mitotic and early G1 cells
  • putative upregulated c-Myc target gene
  • G2 phase CCNA1/CDK2 controls the timing of entry into mitosis by controlling the subsequent activation of CCNB/CDK1, but also has an unexpected role in coordinating the activation of CCNB/CDK1 at the centrosome and in the nucleus
  • is the only essential cell cycle CDK (in the absence of interphase Cdks, CDC2 can execute all the events that are required to drive cell division)
  • can activate CDC25C
  • phosphorylates ELAVL1 during G2, thereby helping to retain it in the nucleus in association with 14-3-3 and hindering its post-transcriptional function and anti-apoptotic influence
  • essential for DNA replication downstream formation of replication initiation complexes in hepatocytes but not in fibroblasts
  • involved in CDK1 and CDK2-mediated phosphorylation, a key mechanism governing EZH2 function
  • promote interphase nuclear pore complexes formation in human dividing cells
  • with AURKA and PLK1, participate in a feedback activation loop and activation of CDK1 initiates the feedback loop activity, leading to rapid and timely entry into mitosis
  • implicated in phosphorylation of CHEK1 which participates in cytoplasmic sequestration of CHEK1 activity
  • CDK1, CDK2, CDK5, can phosphorylate human DNMT1 at Ser154, suggesting an important role for CDKs in controlling DNA methylation patterns in mammalian cells
  • robust timing and ordering of cell cycle events depend on gradual changes in the substrate specificity of CDK1
  • CDK1 and AURKB cooperatively modulate microtubule dynamics and AURKB-dependent phosphorylation of INCENP controls spindle function by excluding the CPC from spindle regions engaged in microtubule polymerization
  • permits resection by phosphorylation of RBBP8 but also prevents RAD51 binding to the resected ends during M-phase double-strand break repair
  • is a critical regulator of DSB repair in M phase
  • archetypical kinase and a central regulator that drives cells through G2 phase and mitosis
  • essential for cell proliferation and tumorigenesis, it is not required for DNA replication and liver regeneration
  • is redundant for S phase progression, but its loss results in endoreduplication
  • slow increase in CDK1 activity in meiosis I acts as a timing mechanism to allow stable kinetochore-microtubule (K-MT) attachments only after bipolar spindle formation, thus preventing attachment errors
  • activity of CDK1 and PLK1 allows spatiotemporally controlled suppression of TP53BP1 function during mitosis
  • CDK1 is a novel NFAT protein kinase that negatively regulates osteoclast differentiation
  • LONRF1, CDK1, RPL18, GNB2L1 (RACK1), RPL30, and SEC61A1 are crucial components in the diagnosis and treatment of Prostate carcinoma
    • CELLULAR PROCESS cell cycle, division, mitosis
    cell cycle, checkpoint
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component with cyclin A and B1 of the M phase promoting factor (MPF)
  • being a component of the kinase complex that phosphorylates the repetitive C-terminus of RNA polymerase II
  • CDK1/CCNB1 activity shields cells against extrinsic death stimuli and unravel the molecular details of the crosstalk between cell cycle and extrinsic apoptotic pathways
    • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
    • protein
  • proliferating cell nuclear antigen, PCNA (
  • kinase associated phosphatase, KAP (
  • cyclin A1 (
  • protein-tyrosine kinase Lck (
  • cyclin B (
  • Fanconi anemia polypeptide, FAC (
  • indirectly interact with TGFbeta RII via cyclin B2 (
  • LATS, large tumor suppressor, homolog 1 (Drosophila), LATS1 (
  • Cyclin B1 (
  • promyelocytic leukemia zinc finger, PLZF (
  • Myt1 (
  • survivin (
  • p53 (
  • Hamartin and tuberin (
  • FEZ1/LZTS1 (
  • CCAAT displacement protein (CDP)/Cux transcription factor (
  • response gene to complement 32 protein, RGC32 (
  • Gadd45b and Gadd45g (
  • WARTS protein kinase (
  • Disabled-2, Dab2 (
  • separase (
  • inactivation of EEF2K by CDK1 may serve to keep EEF2 active during mitosis (where calcium levels rise) and thereby permit protein synthesis to proceed in mitotic cells
  • CDK1 bind to RALBP1 during mitosis, such that endocytosis is inhibited (increased expression of CDK1 inhibits transport function of RALBP1 and promotes apoptosis)
  • different levels of CCNB1-CDK1 kinase activity trigger different mitotic events, thus revealing how the remarkable reorganization of the cell is coordinated at mitotic entry
  • KMT2E is a novel cellular target of CDK1, and the phosphorylation of KMT2E may have an indispensable role in the mitotic progression
  • combined action of CDK1, NEK6, NEK7, and likely other kinases contributes to hyperphosphorylation of NUP98 during mitosis (
  • CEP63 binds to and recruits CDK1 to centrosomes, and thereby regulates mitotic entry (
  • positive feedback in Cdk1 activation serves to overcome the activity of Cdk-opposing phosphatases and thus sustains forward progression in mitosis (
  • initial phase of chromosome condensation requires CDK1-mediated phosphorylation of the NCAPD3 subunit of condensin II
  • CDK1/CCNB1-dependent hyper-phosphorylation of BCL2L11 during prolonged mitotic arrest is an important cell death signal
  • as cells progress through S phase, CCNA2 initially forms complexes with CDK2, and, later, most CCNA2 molecules are bound to CDK1
  • PBK act as a substrate for CDK1
  • during mitosis the kinetochore (KT)-microtubule (MT)-associated protein CLASP2 is progressively and distinctively phosphorylated by CDK1 and PLK1 kinases, concomitant with the establishment of KT-MT attachments
  • CDK1 and POU5F1 interplay to inhibit ES cell differentiation into trophectoderm and thereby maintain stemness
  • UCHL1 physically interacts with CDK1, CDK4, and CDK5, enhancing their kinase activity
  • CDKN3 dephosphorylates threonine-161 of CDK1 during mitotic exit
  • AURKB and CDK1 mediate WAPL activation and release of acetylated cohesin from chromosomes by phosphorylating CDC5A
  • PIN1 interacts with SEPT9 upon mitotic phosphorylation at Thr-24 by CDK1
  • ENSA is regulated by a coherent feed-forward loop as well: CDK1 both activates the phosphorylation (via MASTL) and inhibits the dephosphorylation (via CTDP1) of ENSA
  • mitotic phosphorylation of TP53BP1 by PLK1 and CDK1 that impairs the ability of TP53BP1 to bind the ubiquitinated H2A and to properly localize to the sites of DNA damage
  • CDK1-induced DES phosphorylation is required for efficient separation of desmin-intermediate filament (IF) and generally detected in muscular mitotic cells and generally detected in muscular mitotic cells
  • new role for PTPRF in regulating CDK1 activity and hence cell adhesion to the extracellular matrix
  • VGLL4 is phosphorylated by CDK1 during antimitotic drug-induced mitotic arrest and also in normal mitosis
  • PPP1R12A localization to kinetochores depends on CCNA1/CDK1 activity and PPP1R12A destabilizes kinetochore microtubule (k-MT) attachments by negatively regulating PLK1 at kinetochores
  • CDK1 is a novel NFAT protein kinase that inhibits NFATC1 activation by direct phosphorylation of the NFATC1 S263 residue
  • DDX21 interacted with WDR5 to promote colorectal cancer cell proliferation by activating CDK1 expression
  • ZNF655 played an important role in promoting the binding of E2F transcription factor 1 (E2F1) to the cyclin-dependent kinase 1 (CDK1) promoter
    • cell & other
    REGULATION
    activated by
  • phosphorylation of the threonine T161
    • inhibited by
  • through phosphorylation on Y15 by WEE1, phosphorylation of Y15 has a key role in radiation-induced G2 delay
  • phosphorylation of tyrosine Y15 and threonine T14 by CDK7
  • onset of the anaphase
    • Phosphorylated by
  • increasig of WEE1 and PKMYT1 and the reduction of CDK1 and CCNB1 are involved in 1,25[OH]2VD3-induced G2/M arrest of keratinocyte (
  • casein kinase II, CKII (
  • myelin transcription factor 1, MYT1 (
    • MYT1 and WEE1, that can phosphorylate CDK1
    Other
  • maintained in an inactive state by phosphorylation of WEE1 and MYT1
    • ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    cells lacking CDK1 cannot proliferate but instead enter a senescent state and survive in culture medium
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • reliable molecular biomarker for the diagnosis of prostate carcinoma
    • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    potential of CDK1 inhibitors in cancer therapy
    ANIMAL & CELL MODELS