KEGG   PATHWAY: bbuf04110
Entry
bbuf04110                   Pathway                                
Name
Cell cycle - Bufo bufo (common toad)
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
bbuf04110  Cell cycle
bbuf04110

Other DBs
GO: 0000278
Organism
Bufo bufo (common toad) [GN:bbuf]
Gene
120980269  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
121002136  G1/S-specific cyclin-D1-like [KO:K04503]
121007410  CCND2; G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
120996181  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
121000617  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
120995935  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
121003292  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
120980560  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
121009124  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
120998274  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
120991905  histone deacetylase 1-like [KO:K06067] [EC:3.5.1.98]
120995399  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
121005108  E2F1; transcription factor E2F1 [KO:K17454]
121001631  E2F3; transcription factor E2F3 [KO:K06620]
120980153  E2F4; transcription factor E2F4 [KO:K04682]
121001081  E2F5; transcription factor E2F5 [KO:K04682]
120995762  TFDP1; transcription factor Dp-1 [KO:K04683]
120997620  TFDP2; transcription factor Dp-2 [KO:K09392]
120994338  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
121009227  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
120999513  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
120992261  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
120986029  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
120981775  mothers against decapentaplegic homolog 4-like [KO:K04501]
120992204  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
121001196  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
120994613  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
120991543  cyclin-dependent kinase inhibitor 2A-like isoform X1 [KO:K04685]
120987245  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
121004079  cyclin-dependent kinase inhibitor 1B-like isoform X1 [KO:K06624]
120981149  CDKN1C; cyclin-dependent kinase inhibitor 1C isoform X1 [KO:K09993]
120980762  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
121001308  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
120993680  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
121009396  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
121002808  CUL1; cullin-1 isoform X1 [KO:K03347]
120979112  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
120992178  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
120991711  CCNA2; cyclin-A2 [KO:K06627]
120993978  CCNA1; cyclin-A1 [KO:K06627]
121003035  CDC6; cell division control protein 6 homolog [KO:K02213]
120980189  CDT1; DNA replication factor Cdt1 [KO:K10727]
120978661  ORC1; origin recognition complex subunit 1 [KO:K02603]
121007797  origin recognition complex subunit 2-like isoform X1 [KO:K02604]
121007847  origin recognition complex subunit 2-like [KO:K02604]
120998175  ORC3; origin recognition complex subunit 3 [KO:K02605]
121008846  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
121001635  ORC5; origin recognition complex subunit 5 [KO:K02607]
120980530  ORC6; origin recognition complex subunit 6 [KO:K02608]
120979679  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
120997210  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
121002162  maternal DNA replication licensing factor mcm3 [KO:K02541] [EC:5.6.2.3]
121002126  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
121008452  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
121008437  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
121001206  maternal DNA replication licensing factor mcm6 [KO:K02542] [EC:5.6.2.3]
120986540  MCM7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
120988696  CDC45; cell division control protein 45 homolog [KO:K06628]
120985933  TICRR; treslin isoform X1 [KO:K26117]
121001089  mdm2-binding protein [KO:K26116]
120979193  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
121002892  DBF4; protein DBF4 homolog A [KO:K06629]
121004313  DBF4B; protein DBF4 homolog B [KO:K06629]
121003428  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
120990719  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
120978746  G2/mitotic-specific cyclin-B1-like [KO:K05868]
120986379  G2/mitotic-specific cyclin-B2-like [KO:K21770]
120987154  G2/mitotic-specific cyclin-B2-like [KO:K21770]
120990523  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
120978692  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
120997412  YWHAQ; 14-3-3 protein theta [KO:K16197]
121005988  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
121002753  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
120994748  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
120995483  YWHAG; LOW QUALITY PROTEIN: 14-3-3 protein gamma [KO:K16198]
120988769  YWHAH; 14-3-3 protein eta [KO:K16198]
121007775  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
120980376  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
121002682  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
121007848  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
120991370  CCNH; cyclin-H [KO:K06634]
120992404  CDK7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
120998692  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
121009184  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
121003336  CDC27; cell division cycle protein 27 homolog [KO:K03350]
120995986  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
120988577  ANAPC5; anaphase-promoting complex subunit 5 [KO:K03352]
120995705  CDC16; cell division cycle protein 16 homolog [KO:K03353]
120988553  ANAPC7; anaphase-promoting complex subunit 7 [KO:K03354]
120978673  CDC23; cell division cycle protein 23 homolog isoform X1 [KO:K03355]
120990012  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
121005176  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
120977335  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
121009535  ANAPC13; anaphase-promoting complex subunit 13 isoform X1 [KO:K12456]
121000794  ANAPC15; anaphase-promoting complex subunit 15 [KO:K25228]
121003673  ANAPC16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
120979213  CDC20; cell division cycle protein 20 homolog [KO:K03363]
121009052  securin-like [KO:K06635]
121009056  securin-like [KO:K06635]
120986989  PTTG1; securin [KO:K06635]
120996094  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
121006327  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
120977293  SMC1A; structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
121003283  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
121002754  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
120997520  STAG1; LOW QUALITY PROTEIN: cohesin subunit SA-1 [KO:K06671]
121009212  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
120995760  cohesin subunit SA-2-like isoform X1 [KO:K06671]
120977337  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
121004149  DDX11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
120992175  NIPBL; nipped-B-like protein [KO:K06672]
120989357  MAU2; MAU2 chromatid cohesion factor homolog [KO:K11266]
120977597  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
120998947  ESCO2; LOW QUALITY PROTEIN: N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
121001915  ESCO1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
120990259  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
120996301  PDS5B; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
121005992  WAPL; wings apart-like protein homolog [KO:K25163]
120980375  CDCA5; sororin [KO:K17390]
120987268  AURKB; aurora kinase B [KO:K11479] [EC:2.7.11.1]
121001842  SGO1; shugoshin 1 isoform X1 [KO:K11580]
120989650  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
121009402  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
120991822  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
120996511  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
120980895  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
120981840  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
120999486  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
120981948  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
120982864  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform-like [KO:K11584]
120994356  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
120981466  KNL1; kinetochore scaffold 1 [KO:K11542]
120998144  TTK; LOW QUALITY PROTEIN: dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
121007679  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
120989935  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A isoform X1 [KO:K02537]
120999530  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
120981831  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
121004821  BUB3; mitotic checkpoint protein BUB3 [KO:K02180]
120997303  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
121002690  TRIP13; pachytene checkpoint protein 2 homolog isoform X1 [KO:K22399]
120999831  MAD2L1-binding protein [KO:K26093]
120989631  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
120989090  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
120979334  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
120979588  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
121008964  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
121002127  PRKDC; LOW QUALITY PROTEIN: DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
120997790  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
120996370  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
120980585  MDM2; LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
120982885  E3 ubiquitin-protein ligase Mdm2-like [KO:K06643] [EC:2.3.2.27]
120986731  cellular tumor antigen p53-like [KO:K04451]
120991615  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
120989077  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
120979333  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
120986107  PCNA; proliferating cell nuclear antigen [KO:K04802]
121000276  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
120988812  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
121000768  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
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
bbuf03030  DNA replication
bbuf04010  MAPK signaling pathway
bbuf04120  Ubiquitin mediated proteolysis
bbuf04210  Apoptosis
KO pathway
ko04110   
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