Identifiers
cyclin-dependent kinase 2
HUGO:CDK2, HGNC:1771, ENTREZ:1017, GENECARDS:GC12P056360, UNIPROT:P24941??
HUGO:CDK2, HGNC:1771, ENTREZ:1017, UNIPROT:P24941
HUGO:CDK2 HGNC:1771 ENTREZ:1017 UNIPROT:P24941 GENECARDS:CDK2 REACTOME:87018 KEGG:1017 ATLASONC:GC_CDK2 WIKI:CDK2

Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
 EMT Senescence   / EMT_REGULATORS 
 EMT Senescence   / SENESCENCE 
HMC:SUSTAINING_PROLIFERATIVE_SIGNALLING
 Cell Cycle DNA Repair   / G1_CC_PHASE 
 Cell Cycle DNA Repair   / S_CC_PHASE 
HMC:EVADING_GROWTH_SUPPRESSORS
 Survival   / PI3K_AKT_MTOR 

References
PMID:17303408, PMID:18590585, PMID:17660363, PMID:7575488, PMID:15279786
PMID:18636226
PMID:15147722
PMID:14536078

References
em_re1588:( EMT Senescence  ) PMID:MYC stimulates CDK2 activity
em_emtc_emtc_re1276( EMT Senescence  ):
PMID:10197981
PMID:12193595
PMID:16156666
Erk kinases phosphorylate Smad2 and Smad3 at specific sites in the region linking the DNA-binding domain and the transcriptional activation domain.
These sites are separate from the TGFB receptor phosphorylation sites that activate Smad nuclear translocation.
Feedback loop: TGFB activates Ras/Raf/Mek/Erk signaling (PMID:17673906) and Erk reduces TGFB/Smads transcriptional activity.
PMID:15241418
Feedback loop
CDK phosphorylation of Smad3 on Thr8/Thr179/Ser213 inhibits its transcriptional activity and antiproliferative function.
Because cancer cells often contain high levels of CDK activity, diminishing Smad3 activity by CDK phosphorylation may contribute to tumorigenesis and TGFB- resistance in
cancers.
em_re1592( EMT Senescence  ):
PMID:20713526
CDK2 bind and phosphorylate MYC. Both CDK2 and phosphorylated MYC inhibit senescence genes
PMID:11283614
Myc: an ubiquitous mediator of cell growth and proliferation
Myc can both activate and repress transcription, depending on the nature of associated factors
TGFB downregulates Myc to cause cell cycle arrest.
TGFB activates p15INK4B and/or p21CIP1 (inhibitor of CDKs) ==> CDK inhibition by TGFB
TGFB downregulates cdc25A (a phosphatase, activator of CDKs) ==> CDK inhibition by TGFB
PMID:2191300
Interaction of an NF-kappa B-like factor with a site upstream of the c-myc promoter.
PMID:28536364
c-myc is transcriptionally upregulated by NF-??B
PMID:20027199
MYC induces DNA damage throuh an increase in ROS production, innapropriate DNA synthesis and abrogation of DNA repair
MYC supress the activity of anti-apoptotic BCL2 and BCLXL (BCL2L1) genes
MYC in complex with CDK2 alone inhibit senescence through the inhibition of p16 and p21 expression as well as TERT and BMI1 expression increase. MYC in complex with CDK2 and p27KIP1 induces senescence through the expression increase of p16 and p21 as well as TERT and BMI1 expression decrease. WRN inhibit MYC induced senescence.
PMID:17055429
MYC stimulate P53 and ARF

1. CDK2@Cytosol

1. CDK2@Nucleus

1. CDK2:​p27KIP1*@Cytosol
2. CDK2:​CyclinE1*@Cytosol

1. CDK2:​MYC|​pho@Nucleus
2. CDK2|​Y14/15_pho:​CyclinE*@Nucleus
3. CDK2|​Y14/15_pho:​CyclinA1*@Nucleus
4. (CDK2|​T160_pho:​CyclinE*)|​active@Nucleus
5. (CDK2|​T160_pho:​CyclinA1*)|​active@Nucleus
6. CDK2|​T160_pho|​Y14/15_pho:​CyclinE*@Nucleus
7. CDK2|​T160_pho|​Y14/15_pho:​CyclinA1*@Nucleus
8. CDK2:​MYC:​p27KIP1*@Nucleus

1. CDK2@Nucleus + CyclinA1*@Nucleus → ce_s3123
2. ce_s3123 → CDK2@Nucleus + CyclinA1*@Nucleus
3. ce_s3119 → CDK2|​Y14/15_pho:​CyclinE*@Nucleus
4. CDK2|​Y14/15_pho:​CyclinE*@Nucleus → CDK2|​T160_pho|​Y14/15_pho:​CyclinE*@Nucleus
5. CyclinE*@Nucleus + CDK2@Nucleus → ce_s3119
6. CDK2|​T160_pho|​Y14/15_pho:​CyclinE*@Nucleus → (CDK2|​T160_pho:​CyclinE*)|​active@Nucleus
7. ce_s3119 → CyclinE*@Nucleus + CDK2@Nucleus
8. ce_s3123 → CDK2|​Y14/15_pho:​CyclinA1*@Nucleus
9. CDK2|​Y14/15_pho:​CyclinA1*@Nucleus → CDK2|​T160_pho|​Y14/15_pho:​CyclinA1*@Nucleus
10. CDK2|​T160_pho|​Y14/15_pho:​CyclinA1*@Nucleus → (CDK2|​T160_pho:​CyclinA1*)|​active@Nucleus
11. CDK2@Cytosol + CyclinE1*@Cytosol → CDK2:​CyclinE1*@Cytosol
12. CDK2:​CyclinE1*@Cytosol → Early to mid-G1 phase@Cytosol
13. CDK2_4*@Cytosol → CDK2@Cytosol
14. rCDK2@Nucleus → CDK2@Cytosol
15. MYC@Nucleus + CDK2@Cytosol → CDK2:​MYC|​pho@Nucleus
16. p27KIP1*@Cytosol + CDK2@Cytosol → CDK2:​p27KIP1*@Cytosol
17. CDK2:​p27KIP1*@Cytosol + MYC@Nucleus → CDK2:​MYC:​p27KIP1*@Nucleus
18. ce_s3119 + CDK2@Nucleus + p27KIP1*|​pho@Nucleus → su_akt1_s_akt2_s96

1. G1 phase@Nucleus → S phase@Nucleus
2. S phase@Nucleus → G2 phase@Nucleus
3. E2F1:​RB1@Nucleus → E2F1:​RB1|​pho@Nucleus
4. APC1*:​APC10*:​APC11*:​APC12*:​APC2*:​APC3*:​APC4*:​APC5*:​APC6*:​APC7*:​APC8*:​E-Cadherin*@Nucleus → APC1*:​APC10*:​APC11*:​APC12*:​APC2*:​APC3*:​APC4*:​APC5*:​APC6*:​APC7*:​APC8*:​E-Cadherin*|​pho@Nucleus
5. E2F4_5*:​p107*@Nucleus → E2F4_5*:​p107*|​pho@Nucleus
6. CIP1_KIP1*@Nucleus → degraded
7. ORC4*@Nucleus + ORC5*@Nucleus + ORC6*@Nucleus + ORC3*@Nucleus + ORC2*@Nucleus + ORC1*@Nucleus → ORC1*:​ORC2*:​ORC3*:​ORC4*:​ORC5*:​ORC6*@Nucleus
8. MCM5@Nucleus + MCM6@Nucleus + MCM7@Nucleus + MCM2@Nucleus + MCM3@Nucleus + MCM4@Nucleus → MCM2:​MCM3:​MCM4:​MCM5:​MCM6:​MCM7@Nucleus
9. ORC1*:​ORC2*:​ORC3*:​ORC4*:​ORC5*:​ORC6*@Nucleus + MCM2:​MCM3:​MCM4:​MCM5:​MCM6:​MCM7@Nucleus + CDT1@Nucleus + CDC6@Nucleus + CDC45@Nucleus + POLA*@Nucleus + PRIM*@Nucleus + RPA1@Nucleus + RPA2@Nucleus + RPA3@Nucleus → CDC45:​CDC6:​CDT1:​MCM2:​MCM3:​MCM4:​MCM5:​MCM6:​MCM7:​ORC1*:​ORC2*:​ORC3*:​ORC4*:​ORC5*:​ORC6*:​POLA*:​PRIM*@Nucleus
10. FOXO*@Nucleus → FOXO*|​unk@Nucleus
11. gBMI1@Nucleus → rBMI1@Nucleus
12. gCDKN2A@Nucleus → rp16INK4A*@Nucleus
13. SMAD3|​S423_pho|​S425_pho@Cytosol → SMAD3|​T179_pho|​S204_pho|​S208_pho|​S213_pho|​S423_pho|​S425_pho@Cytosol
14. p27KIP1*@Cytosol → p27KIP1*|​pho@Cytosol
15. gp21CIP1*@Nucleus → rp21CIP1*@Nucleus
16. CyclinE1*@Nucleus → degraded
17. gTERT@Nucleus → rTERT@Nucleus