KEGG   PATHWAY: umr04110
Entry
umr04110                    Pathway                                
Name
Cell cycle - Ursus maritimus (polar bear)
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
Pathway map
umr04110  Cell cycle
umr04110

Other DBs
GO: 0000278
Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103656401  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
103656694  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103656765  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X4 [KO:K11584]
103656869  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
103657014  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
103657330  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X5 [KO:K03456]
103657421  TTK; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
103657610  CDC16; cell division cycle protein 16 homolog [KO:K03353]
103657613  TFDP1; transcription factor Dp-1 [KO:K04683]
103657966  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
103657988  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
103658194  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
103658379  ANAPC4; anaphase-promoting complex subunit 4 isoform X2 [KO:K03351]
103658687  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
103658796  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103659105  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
103659236  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
103659733  ORC2; origin recognition complex subunit 2 [KO:K02604]
103659815  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
103660256  TICRR; treslin [KO:K26117]
103660368  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
103660381  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
103660629  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
103660876  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
103661166  ANAPC5; LOW QUALITY PROTEIN: anaphase-promoting complex subunit 5 [KO:K03352]
103661170  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
103661328  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
103661444  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
103661461  E2F5; transcription factor E2F5 isoform X2 [KO:K04682]
103661509  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
103661576  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
103661598  [KO:K26116]
103661697  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
103661735  CDC6; cell division control protein 6 homolog [KO:K02213]
103661788  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A isoform X1 [KO:K02537]
103661798  CCNA2; cyclin-A2 [KO:K06627]
103662311  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
103662421  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
103662531  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
103662875  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
103662903  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
103663135  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
103663314  [KO:K04402]
103663610  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
103663615  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
103663783  CDC25C; M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
103663787  CDC23; cell division cycle protein 23 homolog isoform X1 [KO:K03355]
103663817  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
103663939  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
103664009  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
103664059  [KO:K26093]
103664092  CCND3; G1/S-specific cyclin-D3 isoform X2 [KO:K10152]
103664157  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
103664305  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
103664356  PDS5B; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
103664372  CCNA1; cyclin-A1 [KO:K06627]
103664522  PTTG1; securin isoform X1 [KO:K06635]
103664700  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
103664701  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
103664708  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
103665536  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
103665612  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
103665821  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
103665872  DBF4B; protein DBF4 homolog B [KO:K06629]
103666326  [KO:K06671]
103666443  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
103666654  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
103666767  SFN; 14-3-3 protein sigma [KO:K06644]
103666789  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
103666838  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
103666989  [KO:K06621]
103667175  [KO:K06630]
103667705  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
103667713  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
103667741  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
103667806  ANAPC16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
103667878  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
103668503  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
103668810  [KO:K04498] [EC:2.3.1.48]
103668898  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
103668956  CUL1; cullin-1 [KO:K03347]
103669018  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
103669306  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
103669330  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
103669478  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
103669726  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
103669778  RBL1; retinoblastoma-like protein 1 [KO:K04681]
103670009  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
103670064  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
103670210  YWHAG; 14-3-3 protein gamma [KO:K16198]
103670413  ABL1; tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
103670714  ORC1; origin recognition complex subunit 1 [KO:K02603]
103670732  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
103670813  CDC20; cell division cycle protein 20 homolog [KO:K03363]
103670922  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
103671139  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103671503  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
103671515  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
103672148  CCNH; cyclin-H isoform X1 [KO:K06634]
103672380  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
103672470  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
103672685  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
103673457  KNL1; kinetochore scaffold 1 [KO:K11542]
103673467  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
103673668  E2F4; transcription factor E2F4 [KO:K04682]
103673796  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
103673819  ORC6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
103673959  CDT1; DNA replication factor Cdt1 [KO:K10727]
103674031  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
103674159  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
103674160  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
103674409  PCNA; proliferating cell nuclear antigen [KO:K04802]
103674455  E2F1; transcription factor E2F1 [KO:K17454]
103674532  CDC25B; LOW QUALITY PROTEIN: M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
103674650  ORC5; origin recognition complex subunit 5 isoform X1 [KO:K02607]
103675032  YWHAQ; 14-3-3 protein theta [KO:K16197]
103675112  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
103675144  MAU2; MAU2 chromatid cohesion factor homolog isoform X2 [KO:K11266]
103675234  SMC1A; structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
103675312  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
103675668  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
103675743  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
103675768  DDX11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:3.6.4.13]
103675817  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
103675961  ESCO2; N-acetyltransferase ESCO2 isoform X2 [KO:K11268] [EC:2.3.1.-]
103676555  MCM5; LOW QUALITY PROTEIN: DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
103676798  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
103676974  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
103677394  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
103677406  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
103677407  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
103677688  RB1; retinoblastoma-associated protein [KO:K06618]
103677760  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
103678018  ANAPC15; anaphase-promoting complex subunit 15 isoform X2 [KO:K25228]
103678381  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
103678383  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
103678409  TFDP2; transcription factor Dp-2 isoform X4 [KO:K09392]
103678594  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
103678689  CDKN2D; cyclin-dependent kinase 4 inhibitor D isoform X1 [KO:K06623]
103678785  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
103678831  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
103678944  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
103679154  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
103679240  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
103679434  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
103679442  [KO:K17390]
103679631  SGO1; shugoshin 1 isoform X1 [KO:K11580]
103679831  [KO:K04685]
103680190  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
103680242  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
103681113  YWHAH; 14-3-3 protein eta [KO:K16198]
103681651  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
103681664  [KO:K16197]
103681819  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
103682218  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
103682503  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
121100135  [KO:K04402]
121100753  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
121104811  [KO:K09993]
Reference
PMID:7908906
  Authors
Matsuoka S, Yamaguchi M, Matsukage A
  Title
D-type cyclin-binding regions of proliferating cell nuclear antigen.
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J Biol Chem 269:11030-6 (1994)
Reference
PMID:8242749
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Welch PJ, Wang JY
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A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
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Cell 75:779-90 (1993)
DOI:10.1016/0092-8674(93)90497-E
Reference
PMID:16936746
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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.
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Oncogene 25:5263-7 (2006)
DOI:10.1038/sj.onc.1209680
Reference
PMID:15838516
  Authors
Cobrinik D
  Title
Pocket proteins and cell cycle control.
  Journal
Oncogene 24:2796-809 (2005)
DOI:10.1038/sj.onc.1208619
Reference
PMID:17568790
  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)
DOI:10.1038/nrc2169
Reference
PMID:9832503
  Authors
Diehl JA, Cheng M, Roussel MF, Sherr CJ
  Title
Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization.
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Genes Dev 12:3499-511 (1998)
DOI:10.1101/gad.12.22.3499
Reference
PMID:19020303
  Authors
Klein EA, Assoian RK
  Title
Transcriptional regulation of the cyclin D1 gene at a glance.
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J Cell Sci 121:3853-7 (2008)
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Reference
PMID:10385618
  Authors
Sherr CJ, Roberts JM
  Title
CDK inhibitors: positive and negative regulators of G1-phase progression.
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Genes Dev 13:1501-12 (1999)
DOI:10.1101/gad.13.12.1501
Reference
PMID:12809600
  Authors
Shi Y, Massague J.
  Title
Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
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Cell 113:685-700 (2003)
DOI:10.1016/S0092-8674(03)00432-X
Reference
PMID:12925736
  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.
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Proc Natl Acad Sci U S A 100:10231-6 (2003)
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Reference
PMID:16212951
  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.
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Cardiovasc Res 69:198-206 (2006)
DOI:10.1016/j.cardiores.2005.08.020
Reference
PMID:15838523
  Authors
Harris SL, Levine AJ.
  Title
The p53 pathway: positive and negative feedback loops.
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Oncogene 24:2899-908 (2005)
DOI:10.1038/sj.onc.1208615
Reference
PMID:11099028
  Authors
Vogelstein B, Lane D, Levine AJ
  Title
Surfing the p53 network.
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Nature 408:307-10 (2000)
DOI:10.1038/35042675
Reference
PMID:7973727
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Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O'Connor PM, Fornace AJ Jr
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Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen.
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Science 266:1376-80 (1994)
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Reference
PMID:9889196
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Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization.
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EMBO J 18:396-410 (1999)
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Reference
PMID:17018296
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Sheu YJ, Stillman B
  Title
Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression.
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Mol Cell 24:101-13 (2006)
DOI:10.1016/j.molcel.2006.07.033
Reference
PMID:9029154
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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.
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EMBO J 16:343-54 (1997)
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Reference
PMID:15876871
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  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)
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Reference
PMID:17426725
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Musacchio A, Salmon ED
  Title
The spindle-assembly checkpoint in space and time.
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Nat Rev Mol Cell Biol 8:379-93 (2007)
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Reference
PMID:12573239
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  Title
Chromosome cohesion and separation: from men and molecules.
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Curr Biol 13:R104-14 (2003)
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Reference
PMID:15568976
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Stegmeier F, Amon A
  Title
Closing mitosis: the functions of the Cdc14 phosphatase and its regulation.
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Annu Rev Genet 38:203-32 (2004)
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Reference
PMID:9618481
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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.
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Proc Natl Acad Sci U S A 95:6733-8 (1998)
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Reference
PMID:26650195
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de Boer HR, Guerrero Llobet S, van Vugt MA
  Title
Controlling the response to DNA damage by the APC/C-Cdh1.
  Journal
Cell Mol Life Sci 73:949-60 (2016)
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Reference
PMID:20935501
  Authors
Qiao X, Zhang L, Gamper AM, Fujita T, Wan Y
  Title
APC/C-Cdh1: from cell cycle to cellular differentiation and genomic integrity.
  Journal
Cell Cycle 9:3904-12 (2010)
DOI:10.4161/cc.9.19.13585
Related
pathway
umr03030  DNA replication
umr04010  MAPK signaling pathway
umr04120  Ubiquitin mediated proteolysis
umr04210  Apoptosis
KO pathway
ko04110   

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