General Information of the m6A Target Gene (ID: M6ATAR00209)
Target Name Cyclin-dependent kinase 1 (CDK1)
Synonyms
CDK1; Cell division control protein 2 homolog; Cell division protein kinase 1; p34 protein kinase; CDC2; CDC28A; CDKN1; P34CDC2
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Gene Name CDK1
Chromosomal Location 10q21.2
Family protein kinase superfamily; CMGC Ser/Thr protein kinase family; CDC2/CDKX subfamily
Function
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. 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, KAT5, 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, CGAS 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 (By similarity). CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis. 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. Phosphorylates EML3 at 'Thr-881' which is essential for its interaction with HAUS augmin-like complex and TUBG1. Phosphorylates CGAS during mitosis, leading to its inhibition, thereby preventing CGAS activation by self DNA during mitosis. (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry.
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Gene ID 983
Uniprot ID
CDK1_HUMAN
HGNC ID
HGNC:1722
Ensembl Gene ID
ENSG00000170312
KEGG ID
hsa:983
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
CDK1 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
Methyltransferase-like 3 (METTL3) [WRITER]
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line Liver Mus musculus
Treatment: Mettl3-deficient liver
Control: Wild type liver cells
GSE197800
Regulation
logFC: 2.36E+00
p-value: 3.11E-05
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary circMETTL3 promotes breast cancer progression through circMETTL3/miR-31-5p/Cyclin-dependent kinase 1 (CDK1) axis.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
Pathway Response Cell cycle hsa04110
Cell Process Cell cycle
In-vitro Model BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-10A Normal Homo sapiens CVCL_0598
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
In-vivo Model Twelve female BALB/c nude mice (aged 4 weeks, 18-22g) were randomly divided into 2 groups. Stable circMETTL3-expression SUM1315 cells or control cells (1×106 cells in 0.1 mL PBS) was subcutaneously injected into mammary fat pads of the mice and the growth of tumors was followed up every week. Tumor volume was measured every week using a caliper, calculated as (length × width2)/2. After 4 weeks, mice were sacrificed and checked for final tumor weight.
Protein virilizer homolog (VIRMA) [WRITER]
Representative RNA-seq result indicating the expression of this target gene regulated by VIRMA
Cell Line Human umbilical vein endothelial cells Homo sapiens
Treatment: siVIRMA HUVECs
Control: siControl HUVECs
GSE167067
Regulation
logFC: -7.84E-01
p-value: 3.08E-02
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary KIAA1429 acts as an oncogenic factor in breast cancer by regulating CDK1 in an N6-methyladenosine-independent manner.5'-fluorouracil was found to be very effective in reducing the expression of KIAA1429 and Cyclin-dependent kinase 1 (CDK1) in breast cancer.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
Pathway Response Cell cycle hsa04110
Cell Process Cell proliferation and metastasis
Breast cancer [ICD-11: 2C60]
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary circMETTL3 promotes breast cancer progression through circMETTL3/miR-31-5p/Cyclin-dependent kinase 1 (CDK1) axis.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response Cell cycle hsa04110
Cell Process Cell cycle
In-vitro Model BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
HCC1806 Breast squamous cell carcinoma Homo sapiens CVCL_1258
MCF-10A Normal Homo sapiens CVCL_0598
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MDA-MB-453 Breast adenocarcinoma Homo sapiens CVCL_0418
ZR-75-1 Invasive breast carcinoma Homo sapiens CVCL_0588
In-vivo Model Twelve female BALB/c nude mice (aged 4 weeks, 18-22g) were randomly divided into 2 groups. Stable circMETTL3-expression SUM1315 cells or control cells (1×106 cells in 0.1 mL PBS) was subcutaneously injected into mammary fat pads of the mice and the growth of tumors was followed up every week. Tumor volume was measured every week using a caliper, calculated as (length × width2)/2. After 4 weeks, mice were sacrificed and checked for final tumor weight.
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary KIAA1429 acts as an oncogenic factor in breast cancer by regulating CDK1 in an N6-methyladenosine-independent manner.5'-fluorouracil was found to be very effective in reducing the expression of KIAA1429 and Cyclin-dependent kinase 1 (CDK1) in breast cancer.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Protein virilizer homolog (VIRMA) WRITER
Target Regulation Up regulation
Pathway Response Cell cycle hsa04110
Cell Process Cell proliferation and metastasis
References
Ref 1 CircMETTL3, upregulated in a m6A-dependent manner, promotes breast cancer progression. Int J Biol Sci. 2021 Mar 15;17(5):1178-1190. doi: 10.7150/ijbs.57783. eCollection 2021.
Ref 2 KIAA1429 acts as an oncogenic factor in breast cancer by regulating CDK1 in an N6-methyladenosine-independent manner. Oncogene. 2019 Aug;38(33):6123-6141. doi: 10.1038/s41388-019-0861-z. Epub 2019 Jul 8.