KEGG   PATHWAY: rtem04110
Entry
rtem04110                   Pathway                                
Name
Cell cycle - Rana temporaria (common frog)
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
rtem04110  Cell cycle
rtem04110

Other DBs
GO: 0000278
Organism
Rana temporaria (common frog) [GN:rtem]
Gene
120908970  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
120912291  FZR1; fizzy-related protein homolog [KO:K03364]
120912951  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
120913019  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
120913106  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
120913378  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
120913743  STAG2; cohesin subunit SA-2 [KO:K06671]
120913960  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
120914117  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
120914143  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
120914406  [KO:K12456]
120914914  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
120915138  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
120915169  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
120915510  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
120915700  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
120916056  [KO:K04503]
120916192  [KO:K10500]
120916441  [KO:K03456]
120917038  [KO:K09993]
120917108  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
120917339  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
120917351  CDCA5; sororin [KO:K17390]
120917393  RBL2; retinoblastoma-like protein 2 [KO:K16332]
120917739  E2F4; transcription factor E2F4 [KO:K04682]
120917885  ORC6; origin recognition complex subunit 6 [KO:K02608]
120917898  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
120918302  CDC6; cell division control protein 6 homolog [KO:K02213]
120918504  [KO:K12456]
120918577  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
120918617  RBL1; retinoblastoma-like protein 1 [KO:K04681]
120918653  CCNA2; cyclin-A2 [KO:K06627]
120918662  E2F1; transcription factor E2F1 [KO:K17454]
120918833  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
120918920  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
120919203  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
120919396  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
120919422  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
120920156  KNL1; kinetochore scaffold 1 [KO:K11542]
120920327  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
120920394  [KO:K04501]
120920440  [KO:K12456]
120920731  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
120920853  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform [KO:K11584]
120921794  [KO:K11584]
120921898  ATRX; transcriptional regulator ATRX [KO:K10779]
120924188  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
120924593  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
120926394  TFDP1; transcription factor Dp-1 [KO:K04683]
120926401  [KO:K06671]
120926456  CDC16; cell division cycle protein 16 homolog [KO:K03353]
120926551  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
120926708  YWHAG; 14-3-3 protein gamma isoform X1 [KO:K16198]
120926812  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
120926814  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
120927190  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
120927385  MAU2; MAU2 chromatid cohesion factor homolog [KO:K11266]
120927590  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
120927610  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
120927639  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
120927760  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
120928081  [KO:K11547]
120928084  [KO:K11547]
120928103  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
120928805  CCNB1; G2/mitotic-specific cyclin-B1 isoform X1 [KO:K05868]
120929143  CCNA1; cyclin-A1 [KO:K06627]
120929166  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
120929228  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
120929264  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
120929323  ESPL1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
120929442  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
120929526  CDK2; LOW QUALITY PROTEIN: cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
120929606  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
120930414  [KO:K06623]
120930657  CCNH; cyclin-H [KO:K06634]
120931101  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
120931197  TICRR; treslin [KO:K26117]
120931386  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
120931987  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
120932164  CDC25C; M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
120932167  CDC23; cell division cycle protein 23 homolog [KO:K03355]
120932377  [KO:K06635]
120932379  [KO:K06635]
120932380  [KO:K06635]
120932381  [KO:K06635]
120932382  [KO:K06635]
120932383  [KO:K06635]
120932428  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
120932432  [KO:K04382] [EC:3.1.3.16]
120932645  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
120932688  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:3.6.4.13]
120932886  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
120932928  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
120932990  PCNA; proliferating cell nuclear antigen [KO:K04802]
120933296  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
120933477  ANAPC7; anaphase-promoting complex subunit 7 [KO:K03354]
120933512  MCM7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
120933520  AURKB; aurora kinase B [KO:K11479] [EC:2.7.11.1]
120933577  ANAPC5; anaphase-promoting complex subunit 5 [KO:K03352]
120933851  TP53; cellular tumor antigen p53 [KO:K04451]
120936117  CDC45; cell division control protein 45 homolog [KO:K06628]
120936185  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
120936357  YWHAQ; 14-3-3 protein theta [KO:K16197]
120936407  STAG1; cohesin subunit SA-1 [KO:K06671]
120936451  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
120936632  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
120936889  YWHAH; 14-3-3 protein eta [KO:K16198]
120937063  TTK; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
120937102  ORC3; origin recognition complex subunit 3 [KO:K02605]
120937226  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
120937463  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
120937565  FBXO5; F-box only protein 5 [KO:K10292]
120937680  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
120937686  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
120937894  TGFB2; LOW QUALITY PROTEIN: transforming growth factor beta-2 proprotein [KO:K13376]
120937921  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
120938086  [KO:K26093]
120939912  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
120939948  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
120940250  SGO1; shugoshin 1 isoform X1 [KO:K11580]
120940358  CUL1; cullin-1 isoform X1 [KO:K03347]
120940454  [KO:K02542] [EC:5.6.2.3]
120940473  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
120940759  E2F3; transcription factor E2F3 [KO:K06620]
120940915  ESCO1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
120940957  [KO:K02541] [EC:5.6.2.3]
120940971  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
120940972  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
120941115  ORC5; origin recognition complex subunit 5 [KO:K02607]
120941246  E2F5; transcription factor E2F5 [KO:K04682]
120941365  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
120941429  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
120941475  RAD21; double-strand-break repair protein rad21 homolog isoform X1 [KO:K06670]
120941497  [KO:K26116]
120941525  MYC; myc proto-oncogene protein [KO:K04377]
120941557  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
120941699  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
120941712  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
120941753  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
120942887  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
120943311  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
120943332  [KO:K04498] [EC:2.3.1.48]
120943408  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
120943485  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
120943724  ORC2; origin recognition complex subunit 2 [KO:K02604]
120944124  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
120944144  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
120945069  [KO:K04685]
120945109  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
120945492  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
120945623  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
120945699  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
120945911  ORC1; origin recognition complex subunit 1 [KO:K02603]
120945929  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
120946043  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
120946115  CDC20; cell division cycle protein 20 homolog [KO:K03363]
120946138  [KO:K05868]
120946201  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
120946707  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
120946849  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
120947064  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
120947194  ANAPC16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
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
rtem03030  DNA replication
rtem04010  MAPK signaling pathway
rtem04120  Ubiquitin mediated proteolysis
rtem04210  Apoptosis
KO pathway
ko04110   

DBGET integrated database retrieval system