KEGG   PATHWAY: hsa04110Help
Entry
hsa04110                    Pathway                                

Name
Cell cycle - Homo sapiens (human)
Description
Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. Downstream targets of CDKs include transcription factor E2F and its regulator Rb. Precise activation and inactivation of CDKs at specific points in the cell cycle are required for orderly cell division. Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated.
 Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. p53 and its transcriptional targets play an important role in both G1 and G2 checkpoints. ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation.
Class
Cellular Processes; Cell growth and death
BRITE hierarchy
Pathway map
Cell cycle
hsa04110

All organismsOrtholog table
Module
Origin recognition complex [PATH:hsa04110]
MCM complex [PATH:hsa04110]
DNA-PK complex [PATH:hsa04110]
SCF-SKP2 complex [PATH:hsa04110]
APC/C complex [PATH:hsa04110]
Disease
H00409  
Type II diabetes mellitus
H00631  
Cornelia de Lange syndrome (CdLS)
H00713  
Beckwith-Wiedemann syndrome
H00848  
Ataxia with ocular apraxia (AOA)
H00881  
Li-Fraumeni syndrome
H00992  
Seckel syndrome
H01007  
Choroid plexus papilloma
H01023  
Juvenile polyposis syndrome
H01102  
Pituitary adenomas
H01288  
Mosaic variegated aneuploidy (MVA) syndrome
H01385  
Rienhoff syndrome
Drug
D06320  
Vorinostat (JAN/USAN)
D06413  
Nilotinib hydrochloride hydrate (JAN)
D06637  
Romidepsin (JAN/USAN/INN)
D08870  
Belinostat (USAN/INN)
D08953  
Nilotinib (USAN/INN)
D09338  
Entinostat (USAN/INN)
D09357  
Mocetinostat dihydrobromide (USAN)
D09604  
Dinaciclib (USAN/INN)
D09641  
Mocetinostat (USAN/INN)
D10019  
Panobinostat lactate (JAN)
D10060  
Abexinostat (USAN)
D10084  
Abexinostat hydrochloride (USAN)
D10154  
Rigosertib (USAN)
D10155  
Rigosertib sodium (USAN)
D10182  
Volasertib (USAN)
D10183  
Volasertib trihydrochloride (USAN)
D10319  
Panobinostat (USAN/INN)
D10372  
Palbociclib (USAN)
D10397  
Rabusertib (USAN/INN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
595  
CCND1; cyclin D1 [KO:K04503]
894  
CCND2; cyclin D2 [KO:K10151]
896  
CCND3; cyclin D3 [KO:K10152]
1019  
CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
1021  
CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
5925  
RB1; retinoblastoma 1 [KO:K06618]
5933  
RBL1; retinoblastoma-like 1 [KO:K04681]
5934  
RBL2; retinoblastoma-like 2 [KO:K16332]
25  
ABL1; c-abl oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
3065  
HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
3066  
HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
1869  
E2F1; E2F transcription factor 1 [KO:K17454]
1870  
E2F2; E2F transcription factor 2 [KO:K09389]
1871  
E2F3; E2F transcription factor 3 [KO:K06620]
1874  
E2F4; E2F transcription factor 4, p107/p130-binding [KO:K04682]
1875  
E2F5; E2F transcription factor 5, p130-binding [KO:K04682]
7027  
TFDP1; transcription factor Dp-1 [KO:K04683]
7029  
TFDP2; transcription factor Dp-2 (E2F dimerization partner 2) [KO:K09392]
2932  
GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
7040  
TGFB1; transforming growth factor, beta 1 [KO:K13375]
7042  
TGFB2; transforming growth factor, beta 2 [KO:K13376]
7043  
TGFB3; transforming growth factor, beta 3 [KO:K13377]
4087  
SMAD2; SMAD family member 2 [KO:K04500]
4088  
SMAD3; SMAD family member 3 [KO:K04500]
4089  
SMAD4; SMAD family member 4 [KO:K04501]
4609  
MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
7709  
ZBTB17; zinc finger and BTB domain containing 17 [KO:K10500]
1029  
CDKN2A; cyclin-dependent kinase inhibitor 2A [KO:K06621]
1030  
CDKN2B; cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) [KO:K04685]
1031  
CDKN2C; cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) [KO:K06622]
1032  
CDKN2D; cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) [KO:K06623]
1027  
CDKN1B; cyclin-dependent kinase inhibitor 1B (p27, Kip1) [KO:K06624]
1028  
CDKN1C; cyclin-dependent kinase inhibitor 1C (p57, Kip2) [KO:K09993]
1026  
CDKN1A; cyclin-dependent kinase inhibitor 1A (p21, Cip1) [KO:K06625]
898  
CCNE1; cyclin E1 [KO:K06626]
9134  
CCNE2; cyclin E2 [KO:K06626]
1017  
CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
6500  
SKP1; S-phase kinase-associated protein 1 [KO:K03094]
8454  
CUL1; cullin 1 [KO:K03347]
9978  
RBX1; ring-box 1, E3 ubiquitin protein ligase [KO:K03868]
6502  
SKP2; S-phase kinase-associated protein 2, E3 ubiquitin protein ligase [KO:K03875]
890  
CCNA2; cyclin A2 [KO:K06627]
8900  
CCNA1; cyclin A1 [KO:K06627]
990  
CDC6; cell division cycle 6 [KO:K02213]
8318  
CDC45; cell division cycle 45 [KO:K06628]
8317  
CDC7; cell division cycle 7 [KO:K02214] [EC:2.7.11.1]
10926  
DBF4; DBF4 zinc finger [KO:K06629]
983  
CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.23 2.7.11.22]
891  
CCNB1; cyclin B1 [KO:K05868]
9133  
CCNB2; cyclin B2 [KO:K05868]
85417  
CCNB3; cyclin B3 [KO:K05868]
994  
CDC25B; cell division cycle 25B [KO:K05866] [EC:3.1.3.48]
995  
CDC25C; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
7534  
YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta [KO:K16197]
7529  
YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta [KO:K16197]
10971  
YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta [KO:K16197]
7531  
YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon [KO:K06630]
7533  
YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta [KO:K16198]
7532  
YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma [KO:K16198]
5347  
PLK1; polo-like kinase 1 [KO:K06631] [EC:2.7.11.21]
7465  
WEE1; WEE1 G2 checkpoint kinase [KO:K06632] [EC:2.7.11.1]
494551  
WEE2; WEE1 homolog 2 (S. pombe) [KO:K06632] [EC:2.7.11.1]
9088  
PKMYT1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
902  
CCNH; cyclin H [KO:K06634]
1022  
CDK7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.23 2.7.11.22]
64682  
ANAPC1; anaphase promoting complex subunit 1 [KO:K03348]
29882  
ANAPC2; anaphase promoting complex subunit 2 [KO:K03349]
996  
CDC27; cell division cycle 27 [KO:K03350]
29945  
ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
51433  
ANAPC5; anaphase promoting complex subunit 5 [KO:K03352]
8881  
CDC16; cell division cycle 16 [KO:K03353]
51434  
ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
8697  
CDC23; cell division cycle 23 [KO:K03355]
10393  
ANAPC10; anaphase promoting complex subunit 10 [KO:K03357]
51529  
ANAPC11; anaphase promoting complex subunit 11 [KO:K03358]
246184  
CDC26; cell division cycle 26 [KO:K03359]
25847  
ANAPC13; anaphase promoting complex subunit 13 [KO:K12456]
991  
CDC20; cell division cycle 20 [KO:K03363]
9232  
PTTG1; pituitary tumor-transforming 1 [KO:K06635]
10744  
PTTG2; pituitary tumor-transforming 2 [KO:K06635]
9700  
ESPL1; extra spindle pole bodies homolog 1 (S. cerevisiae) [KO:K02365] [EC:3.4.22.49]
8243  
SMC1A; structural maintenance of chromosomes 1A [KO:K06636]
27127  
SMC1B; structural maintenance of chromosomes 1B [KO:K06636]
9126  
SMC3; structural maintenance of chromosomes 3 [KO:K06669]
10735  
STAG2; stromal antigen 2 [KO:K06671]
10274  
STAG1; stromal antigen 1 [KO:K06671]
5885  
RAD21; RAD21 homolog (S. pombe) [KO:K06670]
7272  
TTK; TTK protein kinase [KO:K08866] [EC:2.7.12.1]
699  
BUB1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
9184  
BUB3; BUB3 mitotic checkpoint protein [KO:K02180]
701  
BUB1B; BUB1 mitotic checkpoint serine/threonine kinase B [KO:K06637] [EC:2.7.11.1]
8379  
MAD1L1; MAD1 mitotic arrest deficient-like 1 (yeast) [KO:K06638]
4085  
MAD2L1; MAD2 mitotic arrest deficient-like 1 (yeast) [KO:K02537]
10459  
MAD2L2; MAD2 mitotic arrest deficient-like 2 (yeast) [KO:K13728]
51343  
FZR1; fizzy/cell division cycle 20 related 1 (Drosophila) [KO:K03364]
8555  
CDC14B; cell division cycle 14B [KO:K06639] [EC:3.1.3.48 3.1.3.16]
8556  
CDC14A; cell division cycle 14A [KO:K06639] [EC:3.1.3.48 3.1.3.16]
545  
ATR; ataxia telangiectasia and Rad3 related [KO:K06640] [EC:2.7.11.1]
472  
ATM; ataxia telangiectasia mutated [KO:K04728] [EC:2.7.11.1]
7157  
TP53; tumor protein p53 [KO:K04451]
1111  
CHEK1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
11200  
CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
1387  
CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033  
EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
5591  
PRKDC; protein kinase, DNA-activated, catalytic polypeptide [KO:K06642] [EC:2.7.11.1]
4193  
MDM2; MDM2 oncogene, E3 ubiquitin protein ligase [KO:K06643] [EC:6.3.2.19]
1647  
GADD45A; growth arrest and DNA-damage-inducible, alpha [KO:K04402]
4616  
GADD45B; growth arrest and DNA-damage-inducible, beta [KO:K04402]
10912  
GADD45G; growth arrest and DNA-damage-inducible, gamma [KO:K04402]
5111  
PCNA; proliferating cell nuclear antigen [KO:K04802]
2810  
SFN; stratifin [KO:K06644]
993  
CDC25A; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
4998  
ORC1; origin recognition complex, subunit 1 [KO:K02603]
4999  
ORC2; origin recognition complex, subunit 2 [KO:K02604]
23595  
ORC3; origin recognition complex, subunit 3 [KO:K02605]
5000  
ORC4; origin recognition complex, subunit 4 [KO:K02606]
5001  
ORC5; origin recognition complex, subunit 5 [KO:K02607]
23594  
ORC6; origin recognition complex, subunit 6 [KO:K02608]
4171  
MCM2; minichromosome maintenance complex component 2 [KO:K02540] [EC:3.6.4.12]
4172  
MCM3; minichromosome maintenance complex component 3 [KO:K02541] [EC:3.6.4.12]
4173  
MCM4; minichromosome maintenance complex component 4 [KO:K02212] [EC:3.6.4.12]
4174  
MCM5; minichromosome maintenance complex component 5 [KO:K02209] [EC:3.6.4.12]
4175  
MCM6; minichromosome maintenance complex component 6 [KO:K02542] [EC:3.6.4.12]
4176  
MCM7; minichromosome maintenance complex component 7 [KO:K02210] [EC:3.6.4.12]
Reference
PMID:7908906
  Authors
Matsuoka S, Yamaguchi M, Matsukage A
  Title
D-type cyclin-binding regions of proliferating cell nuclear antigen.
  Journal
J Biol Chem 269:11030-6 (1994)
Reference
PMID:8242749
  Authors
Welch PJ, Wang JY
  Title
A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
  Journal
Cell 75:779-90 (1993)
Reference
  Authors
Macaluso M, Montanari M, Giordano A
  Title
Rb family proteins as modulators of gene expression and new aspects regarding the interaction with chromatin remodeling enzymes.
  Journal
Oncogene 25:5263-7 (2006)
Reference
  Authors
Cobrinik D
  Title
Pocket proteins and cell cycle control.
  Journal
Oncogene 24:2796-809 (2005)
Reference
  Authors
Boutros R, Lobjois V, Ducommun B
  Title
CDC25 phosphatases in cancer cells: key players? Good targets?
  Journal
Nat Rev Cancer 7:495-507 (2007)
Reference
PMID:9832503
  Authors
Diehl JA, Cheng M, Roussel MF, Sherr CJ
  Title
Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization.
  Journal
Genes Dev 12:3499-511 (1998)
Reference
  Authors
Klein EA, Assoian RK
  Title
Transcriptional regulation of the cyclin D1 gene at a glance.
  Journal
J Cell Sci 121:3853-7 (2008)
Reference
  Authors
Sherr CJ, Roberts JM
  Title
CDK inhibitors: positive and negative regulators of G1-phase progression.
  Journal
Genes Dev 13:1501-12 (1999)
Reference
  Authors
Shi Y, Massague J.
  Title
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
  Journal
Cell 113:685-700 (2003)
Reference
  Authors
Kamura T, Hara T, Kotoshiba S, Yada M, Ishida N, Imaki H, Hatakeyama S, Nakayama K, Nakayama KI
  Title
Degradation of p57Kip2 mediated by SCFSkp2-dependent ubiquitylation.
  Journal
Proc Natl Acad Sci U S A 100:10231-6 (2003)
Reference
  Authors
Bond M, Sala-Newby GB, Wu YJ, Newby AC
  Title
Biphasic effect of p21Cip1 on smooth muscle cell proliferation: role of PI 3-kinase and Skp2-mediated degradation.
  Journal
Cardiovasc Res 69:198-206 (2006)
Reference
  Authors
Harris SL, Levine AJ.
  Title
The p53 pathway: positive and negative feedback loops.
  Journal
Oncogene 24:2899-908 (2005)
Reference
  Authors
Vogelstein B, Lane D, Levine AJ
  Title
Surfing the p53 network.
  Journal
Nature 408:307-10 (2000)
Reference
PMID:7973727
  Authors
Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O'Connor PM, Fornace AJ Jr
  Title
Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen.
  Journal
Science 266:1376-80 (1994)
Reference
PMID:9889196
  Authors
Petersen BO, Lukas J, Sorensen CS, Bartek J, Helin K
  Title
Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization.
  Journal
EMBO J 18:396-410 (1999)
Reference
  Authors
Sheu YJ, Stillman B
  Title
Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression.
  Journal
Mol Cell 24:101-13 (2006)
Reference
PMID:9029154
  Authors
Martinez AM, Afshar M, Martin F, Cavadore JC, Labbe JC, Doree M
  Title
Dual phosphorylation of the T-loop in cdk7: its role in controlling cyclin H binding and CAK activity.
  Journal
EMBO J 16:343-54 (1997)
Reference
  Authors
Lolli G, Johnson LN
  Title
CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control and a target for drugs?
  Journal
Cell Cycle 4:572-7 (2005)
Reference
  Authors
Musacchio A, Salmon ED
  Title
The spindle-assembly checkpoint in space and time.
  Journal
Nat Rev Mol Cell Biol 8:379-93 (2007)
Reference
  Authors
Uhlmann F
  Title
Chromosome cohesion and separation: from men and molecules.
  Journal
Curr Biol 13:R104-14 (2003)
Reference
  Authors
Stegmeier F, Amon A
  Title
Closing mitosis: the functions of the Cdc14 phosphatase and its regulation.
  Journal
Annu Rev Genet 38:203-32 (2004)
Reference
PMID:9618481
  Authors
Moustakas A, Kardassis D
  Title
Regulation of the human p21/WAF1/Cip1 promoter in hepatic cells by functional interactions between Sp1 and Smad family members.
  Journal
Proc Natl Acad Sci U S A 95:6733-8 (1998)
KO pathway
 
LinkDB All DBs

DBGET integrated database retrieval system