KEGG   PATHWAY: sund04110
Entry
sund04110                   Pathway                                
Name
Cell cycle - Sceloporus undulatus (fence lizard)
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
sund04110  Cell cycle
sund04110

Other DBs
GO: 0000278
Organism
Sceloporus undulatus (fence lizard) [GN:sund]
Gene
121914152  ORC6; origin recognition complex subunit 6 [KO:K02608]
121914214  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
121914520  RBL2; retinoblastoma-like protein 2 [KO:K16332]
121914766  [KO:K04498] [EC:2.3.1.48]
121914778  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
121914862  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
121914956  CDT1; LOW QUALITY PROTEIN: DNA replication factor Cdt1 [KO:K10727]
121915025  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
121915255  SFN; 14-3-3 protein sigma [KO:K06644]
121915414  [KO:K13376]
121915422  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
121915475  [KO:K09389]
121915629  ANAPC1; LOW QUALITY PROTEIN: anaphase-promoting complex subunit 1 [KO:K03348]
121915807  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
121915902  CDCA5; sororin [KO:K17390]
121916287  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
121916695  ANAPC5; anaphase-promoting complex subunit 5 [KO:K03352]
121916722  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
121916760  CDC45; cell division control protein 45 homolog [KO:K06628]
121917041  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
121917047  YWHAG; 14-3-3 protein gamma [KO:K16198]
121917289  [KO:K11547]
121917304  [KO:K11268] [EC:2.3.1.-]
121917329  [KO:K11547]
121917347  [KO:K11268] [EC:2.3.1.-]
121917363  [KO:K02605]
121917392  [KO:K08866] [EC:2.7.12.1]
121917475  [KO:K02605]
121917488  [KO:K08866] [EC:2.7.12.1]
121917546  [KO:K13375]
121917598  [KO:K13375]
121918320  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
121918739  [KO:K06624]
121919251  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
121919394  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
121919399  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
121919592  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
121919793  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
121919828  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
121920591  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
121920614  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
121920842  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
121921188  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
121921419  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
121921670  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
121921691  CCNB1; G2/mitotic-specific cyclin-B1 isoform X1 [KO:K05868]
121921692  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
121921737  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
121922119  [KO:K04382] [EC:3.1.3.16]
121922216  NIPBL; nipped-B-like protein [KO:K06672]
121922239  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
121922250  CCNH; cyclin-H isoform X1 [KO:K06634]
121922253  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
121922277  CDC23; LOW QUALITY PROTEIN: cell division cycle protein 23 homolog [KO:K03355]
121922358  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
121922416  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
121922690  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
121922728  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
121922749  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
121923094  [KO:K04685]
121923217  [KO:K04685]
121923265  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
121923561  BUB1; LOW QUALITY PROTEIN: mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
121923659  CDC14B; LOW QUALITY PROTEIN: dual specificity protein phosphatase CDC14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
121924062  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
121924073  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma isoform X1 [KO:K04402]
121924400  PTTG1; securin [KO:K06635]
121924761  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
121924877  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
121924930  [KO:K06671]
121925088  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
121925294  PDS5B; LOW QUALITY PROTEIN: sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
121925382  ANAPC16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
121925504  STAG1; cohesin subunit SA-1 [KO:K06671]
121925685  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
121925732  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
121925747  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
121925965  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
121926211  TFDP2; LOW QUALITY PROTEIN: transcription factor Dp-2 [KO:K09392]
121926443  CCNA1; cyclin-A1 [KO:K06627]
121926777  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
121926800  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
121926848  KNL1; kinetochore scaffold 1 [KO:K11542]
121926944  [KO:K03353]
121927679  ORC1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
121927870  MCM7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
121927935  YWHAQ; 14-3-3 protein theta [KO:K16197]
121928054  [KO:K26116]
121928257  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
121928401  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
121928484  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
121928487  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
121928569  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
121928598  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
121928647  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
121928679  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
121928742  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
121929123  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
121929422  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
121929441  MYC; myc proto-oncogene protein [KO:K04377]
121929510  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
121929554  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
121929761  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
121929821  [KO:K06622]
121929969  MCM4; DNA replication licensing factor MCM4 isoform X1 [KO:K02212] [EC:5.6.2.3]
121930067  CDC20; cell division cycle protein 20 homolog [KO:K03363]
121930243  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
121930473  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
121930743  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
121930774  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
121930802  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
121930987  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:3.6.4.13]
121931424  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
121931474  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
121931745  CDC25B; LOW QUALITY PROTEIN: M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
121931809  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
121931938  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
121931997  WEE2; wee1-like protein kinase 2 isoform X1 [KO:K06632] [EC:2.7.11.1]
121932021  ORC5; origin recognition complex subunit 5 isoform X1 [KO:K02607]
121932202  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
121932304  CCNA2; cyclin-A2 [KO:K06627]
121932531  CUL1; cullin-1 [KO:K03347]
121932555  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
121932601  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
121932724  RB1; LOW QUALITY PROTEIN: retinoblastoma-associated protein [KO:K06618]
121932809  DBF4B; protein DBF4 homolog B [KO:K06629]
121933100  TICRR; treslin [KO:K26117]
121933170  BUB1B; LOW QUALITY PROTEIN: mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
121933171  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
121933295  WEE1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
121933615  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
121933704  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
121934087  [KO:K26093]
121934446  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
121934668  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
121934882  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
121935171  [KO:K11479] [EC:2.7.11.1]
121935226  CDC6; cell division control protein 6 homolog isoform X1 [KO:K02213]
121935243  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
121935353  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
121935472  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
121935483  SGO1; shugoshin 1 isoform X1 [KO:K11580]
121935671  HDAC2; LOW QUALITY PROTEIN: histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
121935776  PCNA; proliferating cell nuclear antigen [KO:K04802]
121936091  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
121936106  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
121936150  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
121936222  FZR1; fizzy-related protein homolog [KO:K03364]
121936292  STAG2; LOW QUALITY PROTEIN: cohesin subunit SA-2 [KO:K06671]
121936304  ABL1; LOW QUALITY PROTEIN: tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
121936325  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
121936354  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
121936636  ATRX; LOW QUALITY PROTEIN: transcriptional regulator ATRX [KO:K10779]
121936666  FBXO5; F-box only protein 5 [KO:K10292]
121936975  [KO:K10152]
121937212  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
121937233  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
121937470  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
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
sund03030  DNA replication
sund04010  MAPK signaling pathway
sund04120  Ubiquitin mediated proteolysis
sund04210  Apoptosis
KO pathway
ko04110   

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