KEGG   PATHWAY: cabi04110
Entry
cabi04110                   Pathway                                
Name
Cell cycle - Chelonoidis abingdonii (Abingdon island giant tortoise)
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
cabi04110  Cell cycle
cabi04110

Other DBs
GO: 0000278
Organism
Chelonoidis abingdonii (Abingdon island giant tortoise) [GN:cabi]
Gene
116814722  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
116815308  STAG2; cohesin subunit SA-2 [KO:K06671]
116815489  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
116815563  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:3.6.4.13]
116815653  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
116815679  CDT1; DNA replication factor Cdt1 [KO:K10727]
116815728  MCM7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
116815741  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
116815838  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
116816023  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
116816063  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
116816065  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
116816225  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
116816357  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
116816387  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
116816423  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
116816430  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
116816612  SGO1; shugoshin 1 [KO:K11580]
116816751  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
116816806  RAD21L1; double-strand-break repair protein rad21-like protein 1 [KO:K06670]
116817063  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
116817160  [KO:K10779]
116817308  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
116817324  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
116817914  ORC1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
116818667  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
116818797  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
116818906  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
116819010  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
116819070  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
116819102  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
116819111  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
116819583  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
116819817  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
116819898  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
116820201  NDC80; kinetochore protein NDC80 homolog isoform X1 [KO:K11547]
116820266  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
116820483  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
116820539  FBXO5; F-box only protein 5 [KO:K10292]
116820635  E2F5; transcription factor E2F5 [KO:K04682]
116821575  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
116821637  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
116821914  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
116822276  CCNA2; cyclin-A2 [KO:K06627]
116822686  WAPL; wings apart-like protein homolog [KO:K25163]
116822839  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
116822890  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
116822977  MTBP; mdm2-binding protein [KO:K26116]
116823071  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform [KO:K11584]
116823115  YWHAQ; 14-3-3 protein theta [KO:K16197]
116823287  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
116823335  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
116823341  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
116823471  YWHAG; 14-3-3 protein gamma [KO:K16198]
116823485  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
116823500  ORC6; origin recognition complex subunit 6 [KO:K02608]
116823885  STAG1; cohesin subunit SA-1 [KO:K06671]
116823989  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
116824433  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
116824574  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
116824608  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
116824757  CCNA1; cyclin-A1 isoform X1 [KO:K06627]
116824842  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
116824867  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
116825530  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
116825719  [KO:K17390]
116825755  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
116825807  CUL1; cullin-1 [KO:K03347]
116825833  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
116825879  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
116826103  [KO:K11479] [EC:2.7.11.1]
116826151  CCNH; cyclin-H [KO:K06634]
116826417  FZR1; fizzy-related protein homolog [KO:K03364]
116826451  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
116826483  [KO:K04685]
116826484  [KO:K04685]
116826501  KNL1; kinetochore scaffold 1 [KO:K11542]
116826528  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
116826543  MYC; myc proto-oncogene protein [KO:K04377]
116826640  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
116826696  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
116827431  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
116827557  YWHAH; 14-3-3 protein eta [KO:K16198]
116827652  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
116827777  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
116827931  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
116828122  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
116828212  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
116828404  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
116828459  PCNA; proliferating cell nuclear antigen [KO:K04802]
116828489  ESPL1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
116828541  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
116828787  [KO:K11547]
116829019  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
116829048  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
116829058  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
116829153  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
116829324  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
116829349  WEE1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
116829358  RB1; retinoblastoma-associated protein [KO:K06618]
116829440  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
116829611  E2F4; transcription factor E2F4 [KO:K04682]
116829872  CDC6; cell division control protein 6 homolog [KO:K02213]
116830010  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
116830055  RBL1; LOW QUALITY PROTEIN: retinoblastoma-like protein 1 [KO:K04681]
116830156  [KO:K06671]
116830298  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
116830982  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
116831079  PDS5A; LOW QUALITY PROTEIN: sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
116831375  CDC27; cell division cycle protein 27 homolog [KO:K03350]
116831531  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
116831628  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
116832125  ANAPC15; anaphase-promoting complex subunit 15 [KO:K25228]
116832532  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
116832564  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
116832667  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
116832740  [KO:K04501]
116832773  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
116832937  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
116833056  CDC20; cell division cycle protein 20 homolog isoform X1 [KO:K03363]
116833109  PTTG1; securin [KO:K06635]
116833193  TP53; cellular tumor antigen p53 [KO:K04451]
116833295  CDC23; cell division cycle protein 23 homolog isoform X1 [KO:K03355]
116833884  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
116833991  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
116834419  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
116834452  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
116834470  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
116834537  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
116835135  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
116835144  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
116835549  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
116836085  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
116836255  CDCA5; sororin [KO:K17390]
116836359  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
116836465  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
116836467  MCM4; DNA replication licensing factor MCM4 isoform X1 [KO:K02212] [EC:5.6.2.3]
116836722  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
116836745  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
116836936  ORC5; origin recognition complex subunit 5 isoform X1 [KO:K02607]
116837376  ESCO2; N-acetyltransferase ESCO2 isoform X1 [KO:K11268] [EC:2.3.1.-]
116837512  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
116837812  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
116837896  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
116837944  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
116838001  SFN; 14-3-3 protein sigma [KO:K06644]
116838033  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
116838036  [KO:K06625]
116838268  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
116839143  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
116839190  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
116839291  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
116839318  MAU2; MAU2 chromatid cohesion factor homolog [KO:K11266]
116839444  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
116839660  AURKB; aurora kinase B [KO:K11479] [EC:2.7.11.1]
116840114  TICRR; treslin isoform X1 [KO:K26117]
116840155  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
116840169  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
116840200  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
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.
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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.
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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.
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EMBO J 18:396-410 (1999)
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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.
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EMBO J 16:343-54 (1997)
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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)
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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)
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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)
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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
cabi03030  DNA replication
cabi04010  MAPK signaling pathway
cabi04120  Ubiquitin mediated proteolysis
cabi04210  Apoptosis
KO pathway
ko04110   

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