KEGG   PATHWAY: rno04110Help
Entry
rno04110                    Pathway                                

Name
Cell cycle - Rattus norvegicus (rat)
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
rno04110

All organismsOrtholog table
Module
Origin recognition complex [PATH:rno04110]
MCM complex [PATH:rno04110]
DNA-PK complex [PATH:rno04110]
SCF-SKP2 complex [PATH:rno04110]
APC/C complex [PATH:rno04110]
Other DBs
BSID: 
GO: 
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
58919  
Ccnd1; cyclin D1 [KO:K04503]
64033  
Ccnd2; cyclin D2 [KO:K10151]
25193  
Ccnd3; cyclin D3 [KO:K10152]
94201  
Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
114483  
Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
24708  
Rb1; retinoblastoma 1 [KO:K06618]
680111  
Rbl1; retinoblastoma-like 1 (p107) [KO:K04681]
81758  
Rbl2; retinoblastoma-like 2 [KO:K16332]
311860  
Abl1; c-abl oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
tyrosine-protein kinase ABL1-like; K06619 abelson tyrosine-protein kinase 1 [EC:2.7.10.2] [KO:K06619] [EC:2.7.10.2]
297893  
Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
84576  
Hdac1l; histone deacetylase 1-like [KO:K06067] [EC:3.5.1.98]
84577  
Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
291105  
E2f3; E2F transcription factor 3 [KO:K06620]
399489  
E2f1; E2F transcription factor 1 [KO:K06620]
684111  
similar to E2F transcription factor 2; K09389 E2F transcription factor 2 [KO:K09389]
116651  
E2f5; E2F transcription factor 5 [KO:K04682]
E2f4; E2F transcription factor 4, p107/p130-binding [KO:K04682]
361178  
MGC112830; similar to transcription factor [KO:K04683]
300947  
Tfdp2; transcription factor Dp-2 (E2F dimerization partner 2) [KO:K09392]
84027  
Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
59086  
Tgfb1; transforming growth factor, beta 1 [KO:K13375]
81809  
Tgfb2; transforming growth factor, beta 2 [KO:K13376]
25717  
Tgfb3; transforming growth factor, beta 3 [KO:K13377]
25631  
Smad3; SMAD family member 3 [KO:K04500]
29357  
Smad2; SMAD family member 2 [KO:K04500]
50554  
Smad4; SMAD family member 4 [KO:K04501]
24577  
Myc; myelocytomatosis oncogene [KO:K04377]
313666  
Zbtb17; zinc finger and BTB domain containing 17 [KO:K10500]
25163  
Cdkn2a; cyclin-dependent kinase inhibitor 2A [KO:K06621]
25164  
Cdkn2b; cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) [KO:K04685]
54238  
Cdkn2c; cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) [KO:K06622]
494444  
Cdkn2d; similar to cyclin-dependent kinase inhibitor 2D [KO:K06623]
83571  
Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
246060  
Cdkn1c; cyclin-dependent kinase inhibitor 1C [KO:K09993]
114851  
Cdkn1a; cyclin-dependent kinase inhibitor 1A [KO:K06625]
362485  
Ccne2; cyclin E2 [KO:K06626]
25729  
Ccne1; cyclin E1 [KO:K06626]
362817  
Cdk2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
287280  
Skp1; S-phase kinase-associated protein 1 [KO:K03094]
362356  
Cul1; cullin 1 [KO:K03347]
300084  
Rbx1; ring-box 1, E3 ubiquitin protein ligase [KO:K03868]
294790  
Skp2; S-phase kinase-associated protein 2, E3 ubiquitin protein ligase [KO:K03875]
114494  
Ccna2; cyclin A2 [KO:K06627]
295052  
Ccna1; cyclin A1 [KO:K06627]
360621  
Cdc6; cell division cycle 6 [KO:K02213]
287961  
Cdc45; cell division cycle 45 [KO:K06628]
360908  
Cdc7; cell division cycle 7 [KO:K02214] [EC:2.7.11.1]
312046  
Dbf4; DBF4 homolog (S. cerevisiae) [KO:K06629]
54237  
Cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.23 2.7.11.22]
25203  
Ccnb1; cyclin B1 [KO:K05868]
363088  
Ccnb2; cyclin B2 [KO:K05868]
317389  
Ccnb3; cyclin B3 [KO:K05868]
171103  
Cdc25b; cell division cycle 25B [KO:K05866] [EC:3.1.3.48]
307511  
Cdc25c; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
25578  
Ywhaz; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide [KO:K16197]
56011  
Ywhab; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta polypeptide [KO:K16197]
25577  
Ywhaq; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta polypeptide [KO:K16197]
29753  
Ywhae; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide [KO:K06630]
25576  
Ywhah; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide [KO:K16198]
56010  
Ywhag; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma polypeptide [KO:K16198]
25515  
Plk1; polo-like kinase 1 [KO:K06631] [EC:2.7.11.21]
308937  
Wee1; wee 1 homolog (S. pombe) [KO:K06632] [EC:2.7.11.1]
502750  
Wee2; WEE1 homolog 2 (S. pombe) [KO:K06632] [EC:2.7.11.1]
287101  
Pkmyt1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
84389  
Ccnh; cyclin H [KO:K06634]
171150  
Cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.23 2.7.11.22]
311412  
Anapc1; anaphase promoting complex subunit 1 [KO:K03348]
296558  
Anapc2; anaphase promoting complex subunit 2 [KO:K03349]
360643  
Cdc27; cell division cycle 27 [KO:K03350]
305420  
Anapc4; anaphase promoting complex subunit 4 [KO:K03351]
288671  
Anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
290875  
Cdc16; cell division cycle 16 [KO:K03353]
304490  
Anapc7; anaphase promoting complex subunit 7 [KO:K03354]
291689  
Cdc23; cell division cycle 23 [KO:K03355]
361389  
Anapc10; anaphase promoting complex subunit 10 [KO:K03357]
498030  
Anapc11; anaphase promoting complex subunit 11 [KO:K03358]
366381  
Cdc26; cell division cycle 26 [KO:K03359]
685029  
Anapc13; anaphase promoting complex subunit 13 [KO:K12456]
64515  
Cdc20; cell division cycle 20 [KO:K03363]
64193  
Pttg1; pituitary tumor-transforming 1 [KO:K06635]
315330  
Espl1; extra spindle pole bodies homolog 1 (S. cerevisiae) [KO:K02365] [EC:3.4.22.49]
300121  
Smc1b; structural maintenance of chromosomes 1B [KO:K06636]
63996  
Smc1a; structural maintenance of chromosomes 1A [KO:K06636]
29486  
Smc3; structural maintenance of chromosomes 3 [KO:K06669]
313304  
Stag2; stromal antigen 2 [KO:K06671]
315958  
Stag1; stromal antigen 1 [KO:K06671]
314949  
Rad21; RAD21 homolog (S. pombe) [KO:K06670]
315852  
Ttk; Ttk protein kinase [KO:K08866] [EC:2.7.12.1]
296137  
Bub1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
361662  
Bub3; budding uninhibited by benzimidazoles 3 homolog (S. cerevisiae) [KO:K02180]
171576  
Bub1b; BUB1 mitotic checkpoint serine/threonine kinase B [KO:K06637] [EC:2.7.11.1]
680006  
Mad1l1; MAD1 mitotic arrest deficient-like 1 (yeast) [KO:K06638]
297176  
Mad2l1; MAD2 mitotic arrest deficient-like 1 (yeast) [KO:K02537]
313702  
Mad2l2; MAD2 mitotic arrest deficient-like 2 (yeast) [KO:K13728]
314642  
Fzr1; fizzy/cell division cycle 20 related 1 (Drosophila) [KO:K03364]
310806  
Cdc14a; cell division cycle 14A [KO:K06639] [EC:3.1.3.48]
361195  
Cdc14b; cell division cycle 14B [KO:K06639] [EC:3.1.3.48]
685055  
Atr; ataxia telangiectasia and Rad3 related [KO:K06640] [EC:2.7.11.1]
300711  
Atm; ataxia telangiectasia mutated [KO:K04728] [EC:2.7.11.1]
24842  
Tp53; tumor protein p53 [KO:K04451]
140583  
Chek1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
114212  
Chek2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
54244  
Crebbp; CREB binding protein [KO:K04498] [EC:2.3.1.48]
170915  
Ep300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
360748  
Prkdc; protein kinase, DNA activated, catalytic polypeptide [KO:K06642] [EC:2.7.11.1]
314856  
Mdm2; p53 E3 ubiquitin protein ligase [KO:K06643] [EC:6.3.2.19]
25112  
Gadd45a; growth arrest and DNA-damage-inducible, alpha [KO:K04402]
291005  
Gadd45g; growth arrest and DNA-damage-inducible, gamma [KO:K04402]
299626  
Gadd45b; growth arrest and DNA-damage-inducible, beta [KO:K04402]
25737  
Pcna; proliferating cell nuclear antigen [KO:K04802]
313017  
Sfn; stratifin [KO:K06644]
298795  
similar to 14-3-3 protein sigma; K06644 stratifin [KO:K06644]
171102  
Cdc25a; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
313479  
Orc1; origin recognition complex, subunit 1 [KO:K02603]
301430  
Orc2; origin recognition complex, subunit 2 [KO:K02604]
313138  
Orc3; origin recognition complex, subunit 3 [KO:K02605]
295596  
Orc4; origin recognition complex, subunit 4 [KO:K02606]
362304  
Orc5; origin recognition complex, subunit 5 [KO:K02607]
291927  
Orc6; origin recognition complex, subunit 6 [KO:K02608]
312538  
Mcm2; minichromosome maintenance complex component 2 [KO:K02540] [EC:3.6.4.12]
316273  
Mcm3; minichromosome maintenance complex component 3 [KO:K02541] [EC:3.6.4.12]
29728  
Mcm4; minichromosome maintenance complex component 4 [KO:K02212] [EC:3.6.4.12]
291885  
Mcm5; minichromosome maintenance complex component 5 [KO:K02209] [EC:3.6.4.12]
29685  
Mcm6; minichromosome maintenance complex component 6 [KO:K02542] [EC:3.6.4.12]
288532  
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
 

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