KEGG   PATHWAY: pflv04110
Entry
pflv04110                   Pathway                                
Name
Cell cycle - Perca flavescens (yellow perch)
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
pflv04110  Cell cycle
pflv04110

Other DBs
GO: 0000278
Organism
Perca flavescens (yellow perch) [GN:pflv]
Gene
114545465  [KO:K04451]
114545586  anapc10; anaphase-promoting complex subunit 10 [KO:K03357]
114545598  ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
114545827  hdac8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
114545828  mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
114546436  tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
114546473  stag1; cohesin subunit SA-1 [KO:K06671]
114546479  bub1b; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
114546572  ywhaq; 14-3-3 protein theta [KO:K16197]
114546592  [KO:K11584]
114546622  ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
114546658  cdc25b; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
114546669  orc3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
114546671  [KO:K06067] [EC:3.5.1.98]
114546735  atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
114546888  e2f2; transcription factor E2F2 isoform X1 [KO:K09389]
114547699  [KO:K06629]
114547784  [KO:K04498] [EC:2.3.1.48]
114547879  anapc16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
114548000  pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
114548008  bub3; mitotic checkpoint protein BUB3 [KO:K02180]
114548108  [KO:K25163]
114548426  cdc6; cell division control protein 6 homolog [KO:K02213]
114548494  [KO:K21770]
114548975  prkdc; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
114549120  myc; myc proto-oncogene protein isoform X1 [KO:K04377]
114549315  cul1; cullin-1 [KO:K03347]
114550023  orc5; origin recognition complex subunit 5 [KO:K02607]
114550043  [KO:K06625]
114550190  [KO:K06624]
114550246  mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
114550465  [KO:K10151]
114550822  orc4; origin recognition complex subunit 4 [KO:K02606]
114551517  [KO:K16198]
114552350  atm; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
114552362  [KO:K13375]
114552439  [KO:K06630]
114552441  [KO:K21770]
114552598  [KO:K21770]
114552613  anapc15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
114552928  ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
114553318  [KO:K03456]
114553807  cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
114553826  [KO:K16197]
114553865  [KO:K10152]
114554047  cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
114554229  espl1; separin [KO:K02365] [EC:3.4.22.49]
114554457  [KO:K06625]
114554690  rbl1; retinoblastoma-like protein 1 [KO:K04681]
114554747  mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
114555079  anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
114555137  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
114555143  [KO:K06672]
114555175  ccnh; cyclin-H [KO:K06634]
114555216  chek2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
114555270  [KO:K04382] [EC:3.1.3.16]
114555564  [KO:K11547]
114555565  cdc20b; cell division cycle protein 20 homolog B [KO:K03363]
114555571  [KO:K04501]
114555572  [KO:K04402]
114555637  cdk7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
114555742  cdc45; cell division control protein 45 homolog [KO:K06628]
114556028  pcna; proliferating cell nuclear antigen [KO:K04802]
114556042  [KO:K04500]
114556203  anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
114556890  dbf4; protein DBF4 homolog A isoform X1 [KO:K06629]
114557020  e2f3; transcription factor E2F3 [KO:K06620]
114557021  [KO:K06626]
114557065  mtbp; mdm2-binding protein [KO:K26116]
114557225  [KO:K16197]
114557393  tgfb2; transforming growth factor beta-2 proprotein [KO:K13376]
114557429  trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
114557597  [KO:K06670]
114557607  [KO:K23605]
114557918  ttk; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
114558280  smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
114558309  [KO:K16197]
114558622  zbtb17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
114558950  mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
114559079  [KO:K06670]
114559356  e2f1; transcription factor E2F1 [KO:K17454]
114559543  [KO:K23605]
114559995  [KO:K16332]
114560008  wee1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
114560148  e2f4; transcription factor E2F4 [KO:K04682]
114560206  ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
114560212  cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
114560217  ddx11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
114560390  [KO:K09993]
114560520  [KO:K06632] [EC:2.7.11.1]
114560541  ticrr; treslin isoform X1 [KO:K26117]
114560618  [KO:K04503]
114560707  ccne1; G1/S-specific cyclin-E1 [KO:K06626]
114560736  [KO:K06636]
114560832  anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
114560924  [KO:K03364]
114561085  rbl2; retinoblastoma-like protein 2 [KO:K04681]
114561116  orc1; origin recognition complex subunit 1 [KO:K02603]
114561312  cdc14a; LOW QUALITY PROTEIN: dual specificity protein phosphatase CDC14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
114561373  [KO:K04402]
114561492  gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
114561874  cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
114562077  anapc4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
114562164  mau2; MAU2 chromatid cohesion factor homolog [KO:K11266]
114562339  [KO:K04382] [EC:3.1.3.16]
114562492  atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
114562674  mcm7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
114562717  [KO:K13376]
114562803  [KO:K11479] [EC:2.7.11.1]
114562896  [KO:K06635]
114562923  [KO:K06671]
114563037  ccna2; cyclin-A2 [KO:K06627]
114563404  [KO:K06671]
114563778  gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
114563871  tfdp1; transcription factor Dp-1 [KO:K04683]
114564231  pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
114564362  [KO:K06671]
114564533  cdc16; cell division cycle protein 16 homolog [KO:K03353]
114564749  [KO:K03363]
114564750  cdc20; cell division cycle protein 20 homolog [KO:K03363]
114564958  [KO:K04682]
114564980  mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
114565084  [KO:K04402]
114565087  [KO:K03364]
114565142  orc2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
114565257  cdc7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
114565462  [KO:K04377]
114565696  [KO:K04498] [EC:2.3.1.48]
114565744  [KO:K03364]
114565894  mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
114566013  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
114566169  [KO:K04682]
114566380  [KO:K06630]
114566426  pds5b; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
114566613  cdc23; LOW QUALITY PROTEIN: cell division cycle protein 23 homolog [KO:K03355]
114566638  [KO:K06671]
114566770  ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
114566919  chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
114566974  smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
114567128  rb1; retinoblastoma-associated protein isoform X1 [KO:K06618]
114567245  skp1; S-phase kinase-associated protein 1 [KO:K03094]
114567247  ccna1; cyclin-A1 isoform X1 [KO:K06627]
114567279  [KO:K10779]
114567308  [KO:K16198]
114567514  [KO:K04685]
114567712  [KO:K06670]
114567898  [KO:K16197]
114568061  cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
114568081  [KO:K04501]
114568106  [KO:K06626]
114568129  sgo1; shugoshin 1 isoform X1 [KO:K11580]
114568189  cdca5; sororin [KO:K17390]
114568232  plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
114568387  [KO:K06067] [EC:3.5.1.98]
114568541  [KO:K06620]
114568885  [KO:K10151]
114568976  crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
114569286  [KO:K04498] [EC:2.3.1.48]
114569615  mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
114569755  [KO:K02091] [EC:2.7.11.22]
114569772  rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
114569799  anapc2; anaphase-promoting complex subunit 2 isoform X1 [KO:K03349]
114569859  cdc27; cell division cycle protein 27 homolog [KO:K03350]
114570489  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
114570708  [KO:K04501]
114570712  ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
114570717  abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
114570772  [KO:K04402]
114571071  skp2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
114571120  [KO:K06672]
114571295  [KO:K04402]
114571526  cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
114571559  mad1l1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
114571575  anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
114571844  mad2l1bp; MAD2L1-binding protein [KO:K26093]
114571856  cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
114572060  anapc1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
114572145  fbxo5; F-box only protein 5 [KO:K10292]
114572172  ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
114572402  wapl; wings apart-like protein homolog [KO:K25163]
114572574  cdt1; DNA replication factor Cdt1 [KO:K10727]
114572693  knl1; kinetochore scaffold 1 [KO:K11542]
114572735  cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
114572999  ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
114573007  [KO:K13377]
114573033  mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
114573044  [KO:K11584]
114573218  esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
114573695  bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [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.
  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
pflv03030  DNA replication
pflv04010  MAPK signaling pathway
pflv04120  Ubiquitin mediated proteolysis
pflv04210  Apoptosis
KO pathway
ko04110   

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