KEGG   PATHWAY: cpoo04110
Entry
cpoo04110                   Pathway                                
Name
Cell cycle - Crocodylus porosus (Australian saltwater crocodile)
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
cpoo04110  Cell cycle
cpoo04110

Other DBs
GO: 0000278
Organism
Crocodylus porosus (Australian saltwater crocodile) [GN:cpoo]
Gene
109305787  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
109306142  [KO:K06671]
109306281  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
109306287  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
109306521  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
109306586  CCNA1; cyclin-A1 isoform X1 [KO:K06627]
109306599  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
109306698  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
109307003  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
109307240  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
109307241  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
109307299  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
109307382  CDC20; cell division cycle protein 20 homolog [KO:K03363]
109307475  ORC1; origin recognition complex subunit 1 [KO:K02603]
109307577  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
109307739  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
109307834  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
109307841  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
109307983  CCNB1; G2/mitotic-specific cyclin-B1 isoform X1 [KO:K05868]
109307988  CDK7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
109308086  CCNH; LOW QUALITY PROTEIN: cyclin-H [KO:K06634]
109308497  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
109308589  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
109308592  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
109308968  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
109309109  TICRR; treslin [KO:K26117]
109309204  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
109309328  CCNA2; cyclin-A2 [KO:K06627]
109309346  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
109309642  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
109309979  PTTG1; securin isoform X1 [KO:K06635]
109310090  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
109310091  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
109310258  CDC23; cell division cycle protein 23 homolog [KO:K03355]
109310259  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
109310373  CDT1; DNA replication factor Cdt1 [KO:K10727]
109310520  RBL2; retinoblastoma-like protein 2 [KO:K16332]
109310560  ORC6; origin recognition complex subunit 6 [KO:K02608]
109310570  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
109310627  SGO1; shugoshin 1 isoform X1 [KO:K11580]
109311269  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
109311502  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
109311848  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
109311951  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
109312092  YWHAQ; 14-3-3 protein theta [KO:K16197]
109312119  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
109312403  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
109312406  MAU2; MAU2 chromatid cohesion factor homolog [KO:K11266]
109312501  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
109312541  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
109312584  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
109312617  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
109312621  ANAPC5; anaphase-promoting complex subunit 5 [KO:K03352]
109312776  CDC45; cell division control protein 45 homolog [KO:K06628]
109312845  YWHAH; 14-3-3 protein eta [KO:K16198]
109313015  CUL1; cullin-1 isoform X1 [KO:K03347]
109313174  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
109313227  E2F1; transcription factor E2F1 [KO:K17454]
109313256  E2F3; transcription factor E2F3 [KO:K06620]
109313282  RAD21L1; double-strand-break repair protein rad21-like protein 1 [KO:K06670]
109313449  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
109313566  STAG2; cohesin subunit SA-2 [KO:K06671]
109313695  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
109313811  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
109313946  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
109314112  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
109314271  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
109314323  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
109314727  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
109314790  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
109314867  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
109315265  STAG1; cohesin subunit SA-1 [KO:K06671]
109315320  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
109315513  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
109315738  ORC5; origin recognition complex subunit 5 [KO:K02607]
109316207  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
109316210  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
109316274  CCND2; G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
109316306  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
109316307  [KO:K06625]
109316332  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
109316478  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:3.6.4.13]
109316519  WEE2; wee1-like protein kinase 2 isoform X1 [KO:K06632] [EC:2.7.11.1]
109316610  MCM5; DNA replication licensing factor MCM5 isoform X1 [KO:K02209] [EC:5.6.2.3]
109316717  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
109316719  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
109316916  YWHAG; 14-3-3 protein gamma [KO:K16198]
109317279  YWHAE; 14-3-3 protein epsilon [KO:K06630]
109317337  PCNA; proliferating cell nuclear antigen [KO:K04802]
109317512  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
109317772  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
109317794  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
109317916  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
109317977  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
109318498  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
109318516  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
109318599  E2F2; transcription factor E2F2 [KO:K09389]
109318630  SFN; 14-3-3 protein sigma [KO:K06644]
109319001  CDC27; cell division cycle protein 27 homolog [KO:K03350]
109319208  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
109319434  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
109319707  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
109319735  TGFB2; transforming growth factor beta-2 [KO:K13376]
109319864  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
109320027  E2F5; transcription factor E2F5 [KO:K04682]
109320104  FBXO5; F-box only protein 5 [KO:K10292]
109320308  CDC6; cell division control protein 6 homolog [KO:K02213]
109320371  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
109320478  FZR1; fizzy-related protein homolog [KO:K03364]
109320537  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
109320592  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
109320655  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
109320856  TGFB3; LOW QUALITY PROTEIN: transforming growth factor beta-3 [KO:K13377]
109321065  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
109321196  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
109321366  KNL1; protein CASC5 [KO:K11542]
109321405  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
109321461  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
109321486  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
109321636  MTBP; mdm2-binding protein [KO:K26116]
109321765  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
109321829  PDS5A; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
109322218  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
109322776  ORC2; origin recognition complex subunit 2 [KO:K02604]
109323071  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
109323072  ORC4; origin recognition complex subunit 4 [KO:K02606]
109323382  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
109323407  ESPL1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
109323522  [KO:K04685]
109323706  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
109323777  [KO:K04685]
109324065  WAPL; wings apart-like protein homolog [KO:K25163]
109324127  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
109324277  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
109324458  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
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
cpoo03030  DNA replication
cpoo04010  MAPK signaling pathway
cpoo04120  Ubiquitin mediated proteolysis
cpoo04210  Apoptosis
KO pathway
ko04110   

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