KEGG   PATHWAY: acs04110
Entry
acs04110                    Pathway                                
Name
Cell cycle - Anolis carolinensis (green anole)
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
acs04110  Cell cycle
acs04110

Other DBs
GO: 0000278
Organism
Anolis carolinensis (green anole) [GN:acs]
Gene
100563772  ccnd1; cyclin D1 [KO:K04503]
100566165  ccnd3; cyclin D3 [KO:K10152]
100559515  cdk4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100558412  cdk6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100567638  rb1; RB transcriptional corepressor 1 [KO:K06618]
100560057  rbl1; RB transcriptional corepressor like 1 [KO:K04681]
100556593  rbl2; RB transcriptional corepressor like 2 [KO:K16332]
100557530  abl1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
100554517  hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
100566341  hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
100562223  e2f1; E2F transcription factor 1 [KO:K17454]
100553413  transcription factor E2F2 [KO:K09389]
100551868  e2f3; E2F transcription factor 3 [KO:K06620]
100557511  e2f4; E2F transcription factor 4 [KO:K04682]
100558534  e2f5; E2F transcription factor 5 [KO:K04682]
100556309  tfdp1; transcription factor Dp-1 [KO:K04683]
100562543  tfdp2; transcription factor Dp-2 [KO:K09392]
100564023  gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
100553920  tgfb1; transforming growth factor beta 1 [KO:K13375]
100568228  tgfb2; transforming growth factor beta 2 [KO:K13376]
100551709  tgfb3; transforming growth factor beta 3 [KO:K13377]
100554929  smad2; SMAD family member 2 [KO:K04500]
100552093  smad4; SMAD family member 4 [KO:K04501]
100558533  myc; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
100557592  zbtb17; zinc finger and BTB domain containing 17 [KO:K10500]
100562668  cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
100556777  cdkn2c; cyclin dependent kinase inhibitor 2C [KO:K06622]
100556102  cdkn2d; cyclin dependent kinase inhibitor 2D [KO:K06623]
100565071  cdkn1b; cyclin dependent kinase inhibitor 1B [KO:K06624]
100565024  cdkn1c; cyclin dependent kinase inhibitor 1C [KO:K06624]
100555337  cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625]
103281026  cyclin-dependent kinase inhibitor 1 [KO:K06625]
100553527  ccne1; cyclin E1 [KO:K06626]
100563792  ccne2; cyclin E2 [KO:K06626]
100555545  cdk2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
100568037  skp1; S-phase kinase associated protein 1 [KO:K03094]
100563024  cul1; cullin 1 [KO:K03347]
100566553  rbx1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
100564206  skp2; S-phase kinase associated protein 2 [KO:K03875]
100558206  ccna1; cyclin A1 [KO:K06627]
100559864  ccna2; cyclin A2 [KO:K06627]
100562161  cdc6; cell division cycle 6 [KO:K02213]
100556551  cdt1; chromatin licensing and DNA replication factor 1 [KO:K10727]
100558146  orc1; origin recognition complex subunit 1 [KO:K02603]
100564675  orc2; origin recognition complex subunit 2 [KO:K02604]
100556490  orc3; origin recognition complex subunit 3 [KO:K02605]
100561974  orc4; origin recognition complex subunit 4 [KO:K02606]
100560062  orc5; origin recognition complex subunit 5 [KO:K02607]
100559533  orc6; origin recognition complex subunit 6 [KO:K02608]
100559976  mcm2; minichromosome maintenance complex component 2 [KO:K02540] [EC:5.6.2.3]
100555447  mcm3; minichromosome maintenance complex component 3 [KO:K02541] [EC:5.6.2.3]
100562294  mcm4; minichromosome maintenance complex component 4 [KO:K02212] [EC:5.6.2.3]
100555411  mcm5; minichromosome maintenance complex component 5 [KO:K02209] [EC:5.6.2.3]
100566917  mcm6; minichromosome maintenance complex component 6 [KO:K02542] [EC:5.6.2.3]
100557004  mcm7; minichromosome maintenance complex component 7 [KO:K02210] [EC:5.6.2.3]
100557246  cdc45; cell division cycle 45 [KO:K06628]
103280616  ticrr; TOPBP1 interacting checkpoint and replication regulator [KO:K26117]
100566628  mtbp; MDM2 binding protein [KO:K26116]
100553179  cdc7; cell division cycle 7 [KO:K02214] [EC:2.7.11.1]
100556057  dbf4; DBF4 zinc finger [KO:K06629]
103279220  dbf4b; DBF4 zinc finger B [KO:K06629]
100562632  cdk1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
100557278  ccnb1; cyclin B1 [KO:K05868]
100562513  ccnb3; cyclin B3 [KO:K21771]
100568149  cdc25b; cell division cycle 25B [KO:K05866] [EC:3.1.3.48]
100565034  cdc25c; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
100553372  ywhaz; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
100556120  ywhab; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
100559510  ywhaq; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
100566139  ywhag; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
100563850  14-3-3 protein gamma-A-like [KO:K16198]
100558384  plk1; polo like kinase 1 [KO:K06631] [EC:2.7.11.21]
100557537  wee1; WEE1 G2 checkpoint kinase [KO:K06632] [EC:2.7.11.1]
100560382  wee2; WEE1 homolog 2 [KO:K06632] [EC:2.7.11.1]
100561512  pkmyt1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
100561616  ccnh; cyclin H [KO:K06634]
100557869  cdk7; cyclin dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
100560934  anapc1; anaphase promoting complex subunit 1 [KO:K03348]
100561087  anapc2; anaphase promoting complex subunit 2 [KO:K03349]
100564328  cdc27; cell division cycle 27 [KO:K03350]
100566439  anapc4; anaphase promoting complex subunit 4 [KO:K03351]
100556933  anapc5; anaphase promoting complex subunit 5 [KO:K03352]
100561033  cdc16; cell division cycle 16 [KO:K03353]
100561057  anapc7; anaphase promoting complex subunit 7 [KO:K03354]
100558072  cdc23; cell division cycle 23 [KO:K03355]
100552925  anapc10; anaphase promoting complex subunit 10 [KO:K03357]
100564838  anapc11; anaphase promoting complex subunit 11 [KO:K03358]
100559425  cdc26; cell division cycle 26 [KO:K03359]
100562213  anapc13; anaphase promoting complex subunit 13 [KO:K12456]
100565539  anapc15; anaphase promoting complex subunit 15 [KO:K25228]
100564116  anapc16; anaphase promoting complex subunit 16 [KO:K25229]
100556314  cdc20; cell division cycle 20 [KO:K03363]
100557187  pttg1; pituitary tumor-transforming 1 [KO:K06635]
100566013  espl1; extra spindle pole bodies like 1, separase [KO:K02365] [EC:3.4.22.49]
100556052  smc1b; structural maintenance of chromosomes 1B [KO:K06636]
100554998  smc1a; structural maintenance of chromosomes 1A [KO:K06636]
100562143  smc3; structural maintenance of chromosomes 3 [KO:K06669]
100551534  rad21; RAD21 cohesin complex component [KO:K06670]
100561517  rad21l1; RAD21 cohesin complex component like 1 [KO:K06670]
100557841  stag2; stromal antigen 2 [KO:K06671]
100559054  stag1; stromal antigen 1 [KO:K06671]
100565959  cohesin subunit SA-2 [KO:K06671]
100561913  atrx; ATRX, chromatin remodeler [KO:K10779]
100561764  ddx11; DEAD/H-box helicase 11 [KO:K11273] [EC:5.6.2.7]
100561843  nipbl; NIPBL, cohesin loading factor [KO:K06672]
100555510  mau2; MAU2 sister chromatid cohesion factor [KO:K11266]
100556612  hdac8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
100559293  esco2; establishment of sister chromatid cohesion N-acetyltransferase 2 [KO:K11268] [EC:2.3.1.-]
100563013  esco1; establishment of sister chromatid cohesion N-acetyltransferase 1 [KO:K11268] [EC:2.3.1.-]
100564256  pds5a; PDS5 cohesin associated factor A [KO:K11267]
100558995  pds5b; PDS5 cohesin associated factor B [KO:K11267]
100553268  wapl; WAPL cohesin release factor [KO:K25163]
103283027  sororin-B-like [KO:K17390]
103282264  sororin-B [KO:K17390]
100557050  aurora kinase C [KO:K11479] [EC:2.7.11.1]
100555610  sgo1; shugoshin 1 [KO:K11580]
100558622  ppp2cb; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
100568233  ppp2ca; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
100567091  ppp2r1a; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
100558617  ppp2r5c; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
100552371  ppp2r5e; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
100556099  ppp2r5a; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
100562671  ppp2r5d; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
100559852  ndc80; NDC80, kinetochore complex component [KO:K11547]
100553859  knl1; kinetochore scaffold 1 [KO:K11542]
100558324  ttk; TTK protein kinase [KO:K08866] [EC:2.7.12.1]
100552348  mad1l1; MAD1 mitotic arrest deficient like 1 [KO:K06679]
100566557  mad2l1; MAD2 mitotic arrest deficient-like 1 (yeast) [KO:K02537]
100551949  bub1b; BUB1 mitotic checkpoint serine/threonine kinase B [KO:K06637] [EC:2.7.11.1]
100557155  bub3; BUB3, mitotic checkpoint protein [KO:K02180]
100559298  bub1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
100552663  trip13; thyroid hormone receptor interactor 13 [KO:K22399]
103282544  mad2l1bp; MAD2L1 binding protein [KO:K26093]
100563583  mtrf1l; mitochondrial translational release factor 1 like [KO:K10292]
100555123  cdc14b; cell division cycle 14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100558012  cdc14a; cell division cycle 14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
100563301  crebbp; CREB binding protein [KO:K04498] [EC:2.3.1.48]
100566746  ep300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
100562493  prkdc; protein kinase, DNA-activated, catalytic polypeptide [KO:K06642] [EC:2.7.11.1]
100561948  atr; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
100556408  serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
100560063  atm; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
100556723  mdm2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
103282543  cellular tumor antigen p53 [KO:K04451]
100554443  gadd45a; growth arrest and DNA damage inducible alpha [KO:K04402]
100567812  gadd45g; growth arrest and DNA damage inducible gamma [KO:K04402]
100560949  pcna; proliferating cell nuclear antigen [KO:K04802]
100555819  sfn; stratifin [KO:K06644]
100564808  chek1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
103280245  M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
100558641  cdc25a; cell division cycle 25A [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
acs03030  DNA replication
acs04010  MAPK signaling pathway
acs04120  Ubiquitin mediated proteolysis
acs04210  Apoptosis
KO pathway
ko04110   
LinkDB

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