KEGG   PATHWAY: opi04110
Entry
opi04110                    Pathway                                
Name
Cell cycle - Ochotona princeps (American pika)
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
opi04110  Cell cycle
opi04110

Other DBs
GO: 0000278
Organism
Ochotona princeps (American pika) [GN:opi]
Gene
101516182  RBL1; retinoblastoma-like protein 1 [KO:K04681]
101516195  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
101516201  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
101516300  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101516438  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
101516528  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
101516556  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
101516715  TICRR; LOW QUALITY PROTEIN: treslin [KO:K26117]
101516800  [KO:K05866] [EC:3.1.3.48]
101516928  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
101517017  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
101517073  [KO:K04498] [EC:2.3.1.48]
101517179  SFN; 14-3-3 protein sigma [KO:K06644]
101517238  ORC6; origin recognition complex subunit 6 [KO:K02608]
101517568  YWHAG; 14-3-3 protein gamma [KO:K16198]
101517612  RB1; retinoblastoma-associated protein [KO:K06618]
101517633  ORC3; origin recognition complex subunit 3 [KO:K02605]
101517797  ESCO1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
101517996  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
101518001  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
101518020  [KO:K03456]
101518320  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
101518404  ORC5; origin recognition complex subunit 5 [KO:K02607]
101518589  DBF4B; protein DBF4 homolog B [KO:K06629]
101518790  CCNB1; G2/mitotic-specific cyclin-B1 isoform X1 [KO:K05868]
101518802  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
101518852  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
101518983  [KO:K03357]
101519009  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
101519018  MDM2; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
101519048  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
101519247  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
101519273  CDK7; cyclin-dependent kinase 7 isoform X2 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
101519285  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
101519394  FZR1; fizzy-related protein homolog isoform X2 [KO:K03364]
101519401  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
101519435  CDC25C; M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
101519504  YWHAQ; 14-3-3 protein theta [KO:K16197]
101519750  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
101519985  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
101520002  E2F4; transcription factor E2F4 [KO:K04682]
101520141  TFDP2; transcription factor Dp-2 [KO:K09392]
101520493  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
101520591  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
101520601  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
101520672  ORC1; origin recognition complex subunit 1 [KO:K02603]
101520975  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
101521166  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101521285  [KO:K06632] [EC:2.7.11.1]
101521309  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
101521330  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
101521356  ORC2; origin recognition complex subunit 2 [KO:K02604]
101521626  PTTG1; securin [KO:K06635]
101521693  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101521701  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
101521724  SGO1; shugoshin 1 [KO:K11580]
101521938  [KO:K25228]
101522267  CDC16; cell division cycle protein 16 homolog [KO:K03353]
101522285  MYC; myc proto-oncogene protein [KO:K04377]
101522311  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
101522364  [KO:K06626]
101522490  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
101522568  [KO:K26093]
101522654  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
101522960  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
101523167  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
101523250  TFDP1; transcription factor Dp-1 [KO:K04683]
101523417  YWHAZ; 14-3-3 protein zeta/delta isoform X1 [KO:K16197]
101523554  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
101524259  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
101524527  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
101524804  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
101524825  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
101524904  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
101525102  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
101525172  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
101525183  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
101525356  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
101525463  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
101525575  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
101525775  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
101526052  TTK; dual specificity protein kinase TTK isoform X3 [KO:K08866] [EC:2.7.12.1]
101526073  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
101526243  E2F5; transcription factor E2F5 [KO:K04682]
101526437  FBXO5; F-box only protein 5 [KO:K10292]
101526626  [KO:K04802]
101526643  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
101526697  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
101526755  YWHAE; 14-3-3 protein epsilon [KO:K06630]
101526971  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
101527008  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
101527160  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
101527218  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
101527626  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101527767  CCNA1; cyclin-A1 [KO:K06627]
101527828  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
101527846  DDX11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:3.6.4.13]
101528096  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
101528309  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
101528335  YWHAH; 14-3-3 protein eta [KO:K16198]
101528346  TP53; cellular tumor antigen p53 [KO:K04451]
101528367  KNL1; kinetochore scaffold 1 [KO:K11542]
101528414  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
101528620  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
101528728  E2F2; transcription factor E2F2 [KO:K09389]
101529104  BUB3; mitotic checkpoint protein BUB3 [KO:K02180]
101529108  [KO:K06067] [EC:3.5.1.98]
101529269  [KO:K26116]
101529376  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
101529396  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
101529567  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
101529581  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
101529633  WEE1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
101529838  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
101529841  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
101529862  E2F1; transcription factor E2F1 [KO:K17454]
101529904  [KO:K13375]
101529995  CUL1; cullin-1 [KO:K03347]
101530078  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
101530358  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
101530437  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
101530537  STAG2; cohesin subunit SA-2 [KO:K06671]
101530622  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
101530634  CDC6; cell division control protein 6 homolog isoform X2 [KO:K02213]
101530682  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
101531026  CDC20; cell division cycle protein 20 homolog [KO:K03363]
101531086  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
101531170  [KO:K16198]
101531289  CCNA2; cyclin-A2 isoform X1 [KO:K06627]
101531393  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
101531401  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
101531600  MCM3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
101531631  CCND1; G1/S-specific cyclin-D1 isoform X2 [KO:K04503]
101531644  [KO:K06621]
101532127  NIPBL; nipped-B-like protein [KO:K06672]
101532400  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101532614  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
101532983  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
101533197  ATRX; transcriptional regulator ATRX [KO:K10779]
101533379  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
101533416  [KO:K06643] [EC:2.3.2.27]
101533693  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101533733  CDT1; DNA replication factor Cdt1 [KO:K10727]
101533794  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
101533918  CDC25B; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
101534121  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
101534166  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
101534381  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
101534457  CDC14A; dual specificity protein phosphatase CDC14A isoform X2 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101534592  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
101534621  CCNH; cyclin-H [KO:K06634]
101534939  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
101535016  ESCO2; LOW QUALITY PROTEIN: N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
101535151  CDCA5; sororin [KO:K17390]
101535218  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
101535239  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
101535531  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X3 [KO:K03456]
101535569  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
101535804  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
101536117  E2F3; transcription factor E2F3 [KO:K06620]
101536380  ORC4; origin recognition complex subunit 4 [KO:K02606]
101536424  CDC23; cell division cycle protein 23 homolog [KO:K03355]
101536457  CDC27; cell division cycle protein 27 homolog [KO:K03350]
101536480  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
101536651  [KO:K04802]
101536666  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
105942564  [KO:K03357]
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)
DOI:10.1016/0092-8674(93)90497-E
Reference
PMID:16936746
  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)
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.
  Journal
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.
  Journal
J Cell Sci 121:3853-7 (2008)
DOI:10.1242/jcs.039131
Reference
PMID:10385618
  Authors
Sherr CJ, Roberts JM
  Title
CDK inhibitors: positive and negative regulators of G1-phase progression.
  Journal
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.
  Journal
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.
  Journal
Proc Natl Acad Sci U S A 100:10231-6 (2003)
DOI:10.1073/pnas.1831009100
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.
  Journal
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.
  Journal
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.
  Journal
Nature 408:307-10 (2000)
DOI:10.1038/35042675
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)
DOI:10.1126/science.7973727
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)
DOI:10.1093/emboj/18.2.396
Reference
PMID:17018296
  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)
DOI:10.1016/j.molcel.2006.07.033
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)
DOI:10.1093/emboj/16.2.343
Reference
PMID:15876871
  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)
DOI:10.4161/cc.4.4.1607
Reference
PMID:17426725
  Authors
Musacchio A, Salmon ED
  Title
The spindle-assembly checkpoint in space and time.
  Journal
Nat Rev Mol Cell Biol 8:379-93 (2007)
DOI:10.1038/nrm2163
Reference
PMID:12573239
  Authors
Uhlmann F
  Title
Chromosome cohesion and separation: from men and molecules.
  Journal
Curr Biol 13:R104-14 (2003)
DOI:10.1016/S0960-9822(03)00039-3
Reference
PMID:15568976
  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)
DOI:10.1146/annurev.genet.38.072902.093051
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)
DOI:10.1073/pnas.95.12.6733
Reference
PMID:26650195
  Authors
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)
DOI:10.1007/s00018-015-2096-7
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
opi03030  DNA replication
opi04010  MAPK signaling pathway
opi04120  Ubiquitin mediated proteolysis
opi04210  Apoptosis
KO pathway
ko04110   

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