CDK1(细胞周期蛋白依赖性激酶1,Cyclin-Dependent Kinase 1)是一种关键的丝氨酸/苏氨酸蛋白激酶,属于CDK基因家族。该家族成员通过结合细胞周期蛋白(Cyclin)调控细胞周期进程,其共性是通过磷酸化下游靶蛋白(如视网膜母细胞瘤蛋白RB)控制细胞周期检查点、DNA复制和分裂。CDK1是其中最重要的成员,主要与Cyclin B1结合形成复合物(MPF,成熟促进因子),驱动细胞从G2期进入M期(有丝分裂期),其活性峰值出现在分裂期,负责调控染色体凝集、纺锤体形成和核膜解体等关键事件。CDK1的作用位点集中在细胞核和细胞质,通过磷酸化组蛋白、核纤层蛋白等靶点执行功能。若CDK1发生功能丧失性突变(如Thr14/Tyr15磷酸化位点突变),会导致细胞周期阻滞在G2/M期,引发基因组不稳定;而过度激活突变(如Thr161磷酸化增强)则可能引起不受控的细胞增殖。CDK1表达异常与多种疾病相关:过表达常见于乳腺癌、肺癌等恶性肿瘤,促进肿瘤细胞快速分裂;而表达不足则导致胚胎发育障碍或组织再生受损。实验表明,CDK1过表达会抑制凋亡基因(如p53)功能并激活增殖信号通路(如Wnt/β-catenin),而敲低CDK1将引发G2/M期停滞并上调p21等周期抑制蛋白。该基因还具有代偿功能——当其他CDK(如CDK2/4/6)被抑制时,CDK1可能被异常激活以维持细胞周期运转,这种特性使其成为癌症治疗的潜在靶点,目前已有CDK1抑制剂(如RO-3306)处于研究阶段。
The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF), which is essential for G1/S and G2/M phase transitions of eukaryotic cell cycle. Mitotic cyclins stably associate with this protein and function as regulatory subunits. The kinase activity of this protein is controlled by cyclin accumulation and destruction through the cell cycle. The phosphorylation and dephosphorylation of this protein also play important regulatory roles in cell cycle control. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
由该基因编码的蛋白质是丝氨酸/苏氨酸蛋白激酶家族的一个成员。这种蛋白是一种称为M相促进因子(MPF),这是至关重要的G1 / S期和G2真核细胞周期/ M期过渡的高度保守的蛋白激酶复合物的催化亚基。有丝分裂细胞周期蛋白稳定地与该蛋白质相关联,并作为调节亚单位。这种蛋白的激酶活性通过细胞周期蛋白的积累和破坏通过细胞周期控制的。磷酸化和dephosphoryl这种蛋白质的通货膨胀也起到细胞周期控制重要的调节作用。已发现该基因编码不同亚型选择性剪接转录变异体。 [由RefSeq的,2009年03月提供]
CDK1基因(以及对应的蛋白质)的细胞分布位置:
CDK1基因的本体(GO)信息:
名称 |
---|
4110 Cell cycle [PATH:hsa04110] |
4114 Oocyte meiosis [PATH:hsa04114] |
4115 p53 signaling pathway [PATH:hsa04115] |
4540 Gap junction [PATH:hsa04540] |
4914 Progesterone-mediated oocyte maturation [PATH:hsa04914] |
5203 Viral carcinogenesis [PATH:hsa05203] |
5168 Herpes simplex infection [PATH:hsa05168] |
5169 Epstein-Barr virus infection [PATH:hsa05169] |
名称 |
---|
Activated TLR4 signalling |
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins |
Activation of NIMA Kinases NEK9, NEK6, NEK7 |
Anchoring of the basal body to the plasma membrane |
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint |
APC/C-mediated degradation of cell cycle proteins |
APC/C:Cdc20 mediated degradation of Cyclin B |
APC/C:Cdc20 mediated degradation of mitotic proteins |
ARMS-mediated activation |
Assembly of the primary cilium |
Axon guidance |
Cdc20:Phospho-APC/C mediated degradation of Cyclin A |
Cell Cycle |
Cell Cycle Checkpoints |
Cell Cycle, Mitotic |
Centrosome maturation |
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex |
Condensation of Prometaphase Chromosomes |
Condensation of Prophase Chromosomes |
Cyclin A/B1 associated events during G2/M transition |
Cyclin B2 mediated events |
Cytokine Signaling in Immune system |
DAP12 interactions |
DAP12 signaling |
Depolymerisation of the Nuclear Lamina |
Developmental Biology |
Downstream signal transduction |
Downstream signaling of activated FGFR1 |
Downstream signaling of activated FGFR2 |
Downstream signaling of activated FGFR3 |
Downstream signaling of activated FGFR4 |
E2F mediated regulation of DNA replication |
E2F-enabled inhibition of pre-replication complex formation |
ERK activation |
ERK1 activation |
Fc epsilon receptor (FCERI) signaling |
FCERI mediated MAPK activation |
FRS-mediated FGFR1 signaling |
FRS-mediated FGFR2 signaling |
FRS-mediated FGFR3 signaling |
Frs2-mediated activation |
FRS2-mediated FGFR4 signaling |
G0 and Early G1 |
G1/S Transition |
G1/S-Specific Transcription |
G2/M Checkpoints |
G2/M DNA damage checkpoint |
G2/M DNA replication checkpoint |
G2/M Transition |
Gastrin-CREB signalling pathway via PKC and MAPK |
Golgi Cisternae Pericentriolar Stack Reorganization |
GRB2 events in EGFR signaling |
GRB2 events in ERBB2 signaling |
IGF1R signaling cascade |
Immune System |
Innate Immune System |
Insulin receptor signalling cascade |
Interleukin-2 signaling |
IRS-mediated signalling |
IRS-related events |
IRS-related events triggered by IGF1R |
Loss of Nlp from mitotic centrosomes |
Loss of proteins required for interphase microtubule organization from the centrosome |
M Phase |
MAP kinase activation in TLR cascade |
MASTL Facilitates Mitotic Progression |
Mitotic G1-G1/S phases |
Mitotic G2-G2/M phases |
Mitotic Prometaphase |
Mitotic Prophase |
MyD88 cascade initiated on plasma membrane |
MyD88 dependent cascade initiated on endosome |
MyD88-independent TLR3/TLR4 cascade |
MyD88:Mal cascade initiated on plasma membrane |
NCAM signaling for neurite out-growth |
NGF signalling via TRKA from the plasma membrane |
Nuclear Envelope Breakdown |
Nuclear Pore Complex (NPC) Disassembly |
Organelle biogenesis and maintenance |
Phosphorylation of Emi1 |
Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes |
Phosphorylation of the APC/C |
Prolonged ERK activation events |
RAF/MAP kinase cascade |
Recruitment of mitotic centrosome proteins and complexes |
Recruitment of NuMA to mitotic centrosomes |
Regulation of APC/C activators between G1/S and early anaphase |
Regulation of mitotic cell cycle |
Regulation of PLK1 Activity at G2/M Transition |
Resolution of Sister Chromatid Cohesion |
SHC-mediated signalling |
SHC-related events |
SHC-related events triggered by IGF1R |
SHC1 events in EGFR signaling |
SHC1 events in ERBB2 signaling |
SHC1 events in ERBB4 signaling |
Signal Transduction |
Signaling by EGFR |
Signaling by ERBB2 |
Signaling by ERBB4 |
Signaling by FGFR |
Signaling by FGFR1 |
Signaling by FGFR2 |
Signaling by FGFR3 |
Signaling by FGFR4 |
Signaling by GPCR |
Signaling by Insulin receptor |
Signaling by Interleukins |
Signaling by Leptin |
Signaling by PDGF |
Signaling by SCF-KIT |
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) |
Signaling by VEGF |
Signalling by NGF |
Signalling to ERKs |
Signalling to p38 via RIT and RIN |
Signalling to RAS |
SOS-mediated signalling |
Toll Like Receptor 10 (TLR10) Cascade |
Toll Like Receptor 2 (TLR2) Cascade |
Toll Like Receptor 3 (TLR3) Cascade |
Toll Like Receptor 4 (TLR4) Cascade |
Toll Like Receptor 5 (TLR5) Cascade |
Toll Like Receptor 7/8 (TLR7/8) Cascade |
Toll Like Receptor 9 (TLR9) Cascade |
Toll Like Receptor TLR1:TLR2 Cascade |
Toll Like Receptor TLR6:TLR2 Cascade |
Toll-Like Receptors Cascades |
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation |
TRAF6 Mediated Induction of proinflammatory cytokines |
TRIF-mediated TLR3/TLR4 signaling |
VEGFA-VEGFR2 Pathway |
VEGFR2 mediated cell proliferation |
疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
Diffuse Large B-Cell Lymphoma | 0.120542884 | 2 | 0 | BeFree_CTD_human |
IGA Glomerulonephritis | 0.12 | 1 | 0 | CTD_human |
Liver carcinoma | 0.088977445 | 16 | 0 | BeFree_LHGDN_RGD |
Thyroid Neoplasm | 0.08 | 1 | 0 | RGD |
Alzheimer's Disease | 0.015373836 | 6 | 0 | BeFree_GAD_LHGDN |
Malignant neoplasm of breast | 0.008262808 | 15 | 0 | BeFree_GAD |
Prostatic Neoplasms | 0.005720142 | 3 | 0 | BeFree_LHGDN |
Colorectal Neoplasms | 0.005720142 | 3 | 0 | BeFree_LHGDN |
Glioma | 0.00408156 | 5 | 0 | BeFree_LHGDN |
Neoplasm Metastasis | 0.003538676 | 4 | 0 | BeFree_LHGDN |
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