KEGG   PATHWAY: cpic04110
Entry
cpic04110                   Pathway                                
Name
Cell cycle - Chrysemys picta (western painted turtle)
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
cpic04110  Cell cycle
cpic04110

Other DBs
GO: 0000278
Organism
Chrysemys picta (western painted turtle) [GN:cpic]
Gene
101943958  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
101940970  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
101943854  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
122174366  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
101930889  RB1; retinoblastoma-associated protein isoform X2 [KO:K06618]
101935739  RBL1; retinoblastoma-like protein 1 isoform X3 [KO:K04681]
101945444  RBL2; LOW QUALITY PROTEIN: retinoblastoma-like protein 2 [KO:K16332]
101935179  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
101943126  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
101948365  HDAC2; histone deacetylase 2 isoform X2 [KO:K06067] [EC:3.5.1.98]
101946215  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
101939699  E2F2; transcription factor E2F2 [KO:K09389]
101939961  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
101940039  E2F5; transcription factor E2F5 [KO:K04682]
101935045  E2F4; transcription factor E2F4 [KO:K04682]
101951658  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
101944218  TFDP2; transcription factor Dp-2 isoform X4 [KO:K09392]
101935079  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101937891  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
101945771  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
101941121  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
101939963  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
101949856  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
101946126  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
101944321  mothers against decapentaplegic homolog 4-like isoform X3 [KO:K04501]
101945997  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
101947333  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
101947021  cyclin-dependent kinase 4 inhibitor B-like isoform X1 [KO:K04685]
101946764  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
101931916  CDKN2C; cyclin-dependent kinase 4 inhibitor C isoform X2 [KO:K06622]
101939954  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
101954164  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
101947339  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
101938764  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
101946480  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
101940805  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
101933939  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
101936963  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
101938030  CUL1; cullin-1 isoform X1 [KO:K03347]
101936281  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
101935689  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
101934768  CCNA2; cyclin-A2 [KO:K06627]
101951296  CCNA1; cyclin-A1 isoform X2 [KO:K06627]
101951788  CDC6; cell division control protein 6 homolog [KO:K02213]
101939268  CDT1; DNA replication factor Cdt1 isoform X1 [KO:K10727]
101940874  ORC1; origin recognition complex subunit 1 isoform X2 [KO:K02603]
101945895  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
101945944  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
101933155  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
101941607  ORC5; origin recognition complex subunit 5 isoform X2 [KO:K02607]
101935719  ORC6; origin recognition complex subunit 6 [KO:K02608]
101941083  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
101935325  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
101954116  DNA replication licensing factor mcm4 [KO:K02212] [EC:5.6.2.3]
101951254  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
101933477  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
101948290  MCM7; DNA replication licensing factor MCM7 isoform X2 [KO:K02210] [EC:5.6.2.3]
101939959  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
101932450  TICRR; treslin isoform X3 [KO:K26117]
101950046  mdm2-binding protein isoform X1 [KO:K26116]
101953525  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
101940681  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
101944637  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
101938813  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
101931319  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
101949268  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
101939952  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
101951508  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
101952003  CDC25C; LOW QUALITY PROTEIN: M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
101937894  YWHAQ; 14-3-3 protein theta [KO:K16197]
101935492  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
101950695  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
101936599  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
101931819  YWHAG; 14-3-3 protein gamma isoform X1 [KO:K16198]
101947191  YWHAH; 14-3-3 protein eta isoform X1 [KO:K16198]
101943364  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
101930927  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
101944546  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
101938167  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
101950084  CCNH; cyclin-H isoform X1 [KO:K06634]
101952860  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
101934785  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
101939969  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
101931378  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
101949863  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
101942750  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
101942123  CDC16; cell division cycle protein 16 homolog [KO:K03353]
101947224  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
101940314  CDC23; cell division cycle protein 23 homolog isoform X1 [KO:K03355]
101945234  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
101935688  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
101953141  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
101950908  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
101949565  ANAPC15; anaphase-promoting complex subunit 15 [KO:K25228]
101941137  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
101939398  CDC20; cell division cycle protein 20 homolog [KO:K03363]
101945013  PTTG1; securin [KO:K06635]
101941011  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
101946055  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
101945859  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
101953960  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
101942798  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
101944229  RAD21L1; double-strand-break repair protein rad21-like protein 1 [KO:K06670]
101940586  cohesin subunit SA-2-like isoform X1 [KO:K06671]
101931360  STAG1; cohesin subunit SA-1 [KO:K06671]
101937508  STAG2; cohesin subunit SA-2 [KO:K06671]
101944103  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
101934565  DDX11; ATP-dependent DNA helicase DDX11 isoform X4 [KO:K11273] [EC:5.6.2.7]
101938865  NIPBL; nipped-B-like protein isoform X2 [KO:K06672]
101953931  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
101943033  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
101938678  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
101943715  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
101943625  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X4 [KO:K11267]
101935610  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
101935917  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
101939596  CDCA5; sororin [KO:K17390]
101940349  AURKB; aurora kinase B [KO:K11479] [EC:2.7.11.1]
101941316  aurora kinase C-like [KO:K11479] [EC:2.7.11.1]
101947596  SGO1; shugoshin 1 isoform X1 [KO:K11580]
101952365  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101946593  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101952182  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X2 [KO:K11584]
101939783  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
101931478  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
101941621  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
101940422  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
101941729  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
101933426  LOW QUALITY PROTEIN: kinetochore protein NDC80 homolog [KO:K11547]
101937128  KNL1; LOW QUALITY PROTEIN: kinetochore scaffold 1 [KO:K11542]
101944837  TTK; dual specificity protein kinase TTK isoform X2 [KO:K08866] [EC:2.7.12.1]
101931462  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X2 [KO:K06679]
101944183  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
101947496  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B isoform X2 [KO:K13728]
101953667  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
101937025  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
101948684  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
101934693  TRIP13; pachytene checkpoint protein 2 homolog isoform X1 [KO:K22399]
101937745  MAD2L1-binding protein [KO:K26093]
101936298  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
101937652  FBXO5; F-box only protein 5 [KO:K10292]
101939203  CDC14B; dual specificity protein phosphatase CDC14B isoform X3 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101946135  CDC14A; dual specificity protein phosphatase CDC14A isoform X3 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101940582  CREB-binding protein isoform X3 [KO:K04498] [EC:2.3.1.48]
101930946  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101936824  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
101945312  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
101949002  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
101936483  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X4 [KO:K06643] [EC:2.3.2.27]
101942845  TP53; cellular tumor antigen p53 [KO:K04451]
101945778  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101933443  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
101945211  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101934567  PCNA; proliferating cell nuclear antigen [KO:K04802]
101946868  SFN; 14-3-3 protein sigma [KO:K06644]
101933610  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
101952469  CHEK2; serine/threonine-protein kinase Chk2 isoform X5 [KO:K06641] [EC:2.7.11.1]
101944298  CDC25A; M-phase inducer phosphatase 1 isoform X1 [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
cpic03030  DNA replication
cpic04010  MAPK signaling pathway
cpic04120  Ubiquitin mediated proteolysis
cpic04210  Apoptosis
KO pathway
ko04110   
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