KEGG   PATHWAY: shr04110
Entry
shr04110                    Pathway                                
Name
Cell cycle - Sarcophilus harrisii (Tasmanian devil)
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
shr04110  Cell cycle
shr04110

Other DBs
GO: 0000278
Organism
Sarcophilus harrisii (Tasmanian devil) [GN:shr]
Gene
100913322  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
100913325  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
100913480  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
100913510  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
100913659  CDC14B; dual specificity protein phosphatase CDC14B isoform X6 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100913766  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
100914196  RB1; retinoblastoma-associated protein [KO:K06618]
100914332  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
100914474  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100914865  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
100914910  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
100914956  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
100914990  DBF4B; protein DBF4 homolog B [KO:K06629]
100915132  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
100915144  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
100915179  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
100915218  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
100915359  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
100916034  FBXO5; F-box only protein 5 [KO:K10292]
100917017  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
100917397  MAU2; MAU2 chromatid cohesion factor homolog [KO:K11266]
100917462  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100917627  CCNA2; cyclin-A2 [KO:K06627]
100917741  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
100918045  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
100918142  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
100918192  CDC45; cell division control protein 45 homolog [KO:K06628]
100918404  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
100918440  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
100918645  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
100918795  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
100918925  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
100919412  TFDP1; transcription factor Dp-1 isoform X2 [KO:K04683]
100919575  FZR1; fizzy-related protein homolog [KO:K03364]
100919598  AURKB; aurora kinase B isoform X3 [KO:K11479] [EC:2.7.11.1]
100919874  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
100919936  CCNA1; cyclin-A1 isoform X1 [KO:K06627]
100920192  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100920321  [KO:K06643] [EC:2.3.2.27]
100920439  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100920472  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
100920657  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:3.6.4.13]
100920736  ANAPC11; anaphase-promoting complex subunit 11 isoform X2 [KO:K03358]
100920827  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
100920834  ORC5; origin recognition complex subunit 5 [KO:K02607]
100920942  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
100920986  CDC20; LOW QUALITY PROTEIN: cell division cycle protein 20 homolog [KO:K03363]
100921010  [KO:K02365] [EC:3.4.22.49]
100921012  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
100921166  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
100921187  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
100921292  CDC23; cell division cycle protein 23 homolog [KO:K03355]
100921308  MYC; myc proto-oncogene protein [KO:K04377]
100921506  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
100921594  E2F2; transcription factor E2F2 [KO:K09389]
100921735  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
100921764  YWHAH; 14-3-3 protein eta [KO:K16198]
100921786  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
100921980  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
100922263  ORC6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
100922344  ESCO2; N-acetyltransferase ESCO2 isoform X1 [KO:K11268] [EC:2.3.1.-]
100922473  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
100922551  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
100922586  ANAPC10; anaphase-promoting complex subunit 10 isoform X2 [KO:K03357]
100922737  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
100923201  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
100923569  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
100923929  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
100924154  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100924163  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
100924208  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
100924279  [KO:K06635]
100924399  ORC1; origin recognition complex subunit 1 [KO:K02603]
100924438  CDC25C; M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
100924454  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
100924467  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
100924580  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
100924873  PCNA; proliferating cell nuclear antigen [KO:K04802]
100924999  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B isoform X1 [KO:K13728]
100925014  MCM3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
100925167  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
100925406  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
100925631  CDK2; cyclin-dependent kinase 2 isoform X4 [KO:K02206] [EC:2.7.11.22]
100925721  SGO1; shugoshin 1 isoform X2 [KO:K11580]
100925753  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
100926176  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
100926283  CREBBP; CREB-binding protein isoform X2 [KO:K04498] [EC:2.3.1.48]
100926417  CUL1; cullin-1 [KO:K03347]
100926464  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
100926531  YWHAQ; 14-3-3 protein theta [KO:K16197]
100926666  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100926691  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
100926825  ORC2; origin recognition complex subunit 2 [KO:K02604]
100926902  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100927043  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
100927161  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
100927300  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
100927310  CDC25B; M-phase inducer phosphatase 2 isoform X2 [KO:K05866] [EC:3.1.3.48]
100927352  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
100927420  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
100927470  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
100927866  MAD2L1BP; MAD2L1-binding protein isoform X2 [KO:K26093]
100928055  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
100928092  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
100928371  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
100928637  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
100928823  TTK; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
100929022  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
100929092  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
100929095  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
100929189  CDT1; DNA replication factor Cdt1 isoform X1 [KO:K10727]
100929371  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
100929617  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
100930047  ABL1; tyrosine-protein kinase ABL1 isoform X2 [KO:K06619] [EC:2.7.10.2]
100930055  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
100930217  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X7 [KO:K11584]
100930283  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
100930296  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
100930498  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
100930602  ANAPC15; LOW QUALITY PROTEIN: anaphase-promoting complex subunit 15 [KO:K25228]
100930833  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
100930939  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
100930960  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
100931175  TICRR; treslin [KO:K26117]
100931176  CCNB2; G2/mitotic-specific cyclin-B2 isoform X2 [KO:K21770]
100931239  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
100931355  KNL1; kinetochore scaffold 1 [KO:K11542]
100931451  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
100931897  E2F4; transcription factor E2F4 [KO:K04682]
100932148  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
100932330  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
100932455  YWHAG; 14-3-3 protein gamma [KO:K16198]
100932579  CCNH; cyclin-H isoform X1 [KO:K06634]
100932580  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
100932595  NDC80; kinetochore protein NDC80 homolog isoform X1 [KO:K11547]
100932607  TGFB1; LOW QUALITY PROTEIN: transforming growth factor beta-1 proprotein [KO:K13375]
100932648  [KO:K04382] [EC:3.1.3.16]
100932748  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
100932899  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100933145  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
100933433  ANAPC16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
100933451  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
100933542  MTBP; mdm2-binding protein isoform X1 [KO:K26116]
100933550  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
100933648  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
100933824  [KO:K06671]
100934350  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
100934420  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
100934669  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
100935088  PTTG1; securin [KO:K06635]
100935358  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
100935397  CDC6; cell division control protein 6 homolog isoform X2 [KO:K02213]
116419912  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
116421696  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
116422809  SFN; 14-3-3 protein sigma [KO:K06644]
116423727  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
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
shr03030  DNA replication
shr04010  MAPK signaling pathway
shr04120  Ubiquitin mediated proteolysis
shr04210  Apoptosis
KO pathway
ko04110   

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