KEGG   PATHWAY: npr04110
Entry
npr04110                    Pathway                                
Name
Cell cycle - Nanorana parkeri (Xizang Plateau frog)
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
npr04110  Cell cycle
npr04110

Other DBs
GO: 0000278
Organism
Nanorana parkeri (Xizang Plateau frog) [GN:npr]
Gene
108783681  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
108783804  ORC1; origin recognition complex subunit 1 [KO:K02603]
108783816  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
108783986  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
108784107  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
108784132  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
108784231  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
108784502  MTBP; mdm2-binding protein [KO:K26116]
108784730  [KO:K04451]
108784765  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
108784778  BUB3; mitotic checkpoint protein BUB3 [KO:K02180]
108784987  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
108785008  CCNA1; cyclin-A1 [KO:K06627]
108785214  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
108785263  CDCA5; sororin [KO:K17390]
108785270  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
108785313  ORC3; origin recognition complex subunit 3 [KO:K02605]
108785450  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
108786090  [KO:K02541] [EC:5.6.2.3]
108786119  E2F1; transcription factor E2F1 [KO:K17454]
108786199  CDC14B; dual specificity protein phosphatase CDC14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
108786355  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
108786389  E2F3; transcription factor E2F3 [KO:K06620]
108786433  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
108786465  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
108786781  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
108786827  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
108786846  ATM; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
108786962  RAD21L1; double-strand-break repair protein rad21-like protein 1 [KO:K06670]
108787415  CDC45; cell division control protein 45 homolog [KO:K06628]
108787778  YWHAH; 14-3-3 protein eta [KO:K16198]
108787862  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
108787899  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
108788045  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
108788200  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
108788361  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
108788530  ANAPC7; anaphase-promoting complex subunit 7 [KO:K03354]
108788632  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
108788711  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
108788765  STAG2; cohesin subunit SA-2 [KO:K06671]
108788968  MYC; myc proto-oncogene protein [KO:K04377]
108789285  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
108789371  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
108789378  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
108789383  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
108789594  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
108789863  YWHAQ; 14-3-3 protein theta [KO:K16197]
108790033  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
108790099  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
108790122  FBXO5; F-box only protein 5 [KO:K10292]
108790155  TFDP2; transcription factor Dp-2 [KO:K09392]
108790265  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
108790510  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
108790564  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
108790704  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
108790758  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
108791110  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
108791169  CDC20; cell division cycle protein 20 homolog [KO:K03363]
108791201  MCM3; LOW QUALITY PROTEIN: DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
108791338  MCM6; DNA replication licensing factor MCM6 isoform X1 [KO:K02542] [EC:5.6.2.3]
108791415  [KO:K06635]
108791416  [KO:K06635]
108791475  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
108791691  TFDP1; transcription factor Dp-1 [KO:K04683]
108791817  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
108791937  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
108792099  [KO:K09993]
108792127  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
108792131  [KO:K04382] [EC:3.1.3.16]
108792199  ANAPC16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
108792226  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
108792248  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
108792451  RB1; retinoblastoma-associated protein [KO:K06618]
108792651  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
108792688  [KO:K02216] [EC:2.7.11.1]
108793027  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
108793031  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
108793093  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
108793323  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
108793412  [KO:K04503]
108793690  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
108793717  CCNA2; cyclin-A2 [KO:K06627]
108793776  PDS5A; LOW QUALITY PROTEIN: sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
108793783  MCM7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
108793785  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
108794363  CUL1; cullin-1 [KO:K03347]
108794817  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
108794993  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
108795216  CDC6; LOW QUALITY PROTEIN: cell division control protein 6 homolog [KO:K02213]
108795265  CDT1; DNA replication factor Cdt1 [KO:K10727]
108795331  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
108795357  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
108795501  ORC4; origin recognition complex subunit 4 [KO:K02606]
108795520  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
108795586  DBF4; protein DBF4 homolog A [KO:K06629]
108795614  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
108795797  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
108795903  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
108795926  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
108795947  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
108795981  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
108796320  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
108796745  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
108796917  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
108796961  ORC5; origin recognition complex subunit 5 [KO:K02607]
108797290  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
108797534  SMC1A; LOW QUALITY PROTEIN: structural maintenance of chromosomes protein 1A [KO:K06636]
108797557  CDK7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
108797587  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
108797600  CDC25C; M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
108797603  CDC23; cell division cycle protein 23 homolog [KO:K03355]
108797630  SGO1; shugoshin 1 [KO:K11580]
108797984  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
108798152  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
108798402  ORC2; origin recognition complex subunit 2 [KO:K02604]
108798610  [KO:K06671]
108798643  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
108798779  [KO:K03456]
108798842  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
108798855  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
108799278  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
108799649  TICRR; LOW QUALITY PROTEIN: treslin [KO:K26117]
108799687  [KO:K06635]
108799688  [KO:K06635]
108799773  ESCO1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
108799825  [KO:K02542] [EC:5.6.2.3]
108800010  WAPL; wings apart-like protein homolog [KO:K25163]
108800157  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
108800169  PCNA; proliferating cell nuclear antigen [KO:K04802]
108800425  CCNH; cyclin-H [KO:K06634]
108800620  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
108800705  [KO:K06645] [EC:3.1.3.48]
108800768  [KO:K13375]
108800990  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
108801162  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
108801246  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
108801558  [KO:K04685]
108801934  YWHAE; 14-3-3 protein epsilon [KO:K06630]
108802203  [KO:K03364]
108802364  NDC80; LOW QUALITY PROTEIN: kinetochore protein NDC80 homolog [KO:K11547]
108802400  YWHAG; 14-3-3 protein gamma [KO:K16198]
108802495  ANAPC15; anaphase-promoting complex subunit 15 [KO:K25228]
108802626  [KO:K05868]
108802834  [KO:K06632] [EC:2.7.11.1]
108802871  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
108802965  ORC6; origin recognition complex subunit 6 [KO:K02608]
108802990  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
108803114  [KO:K04501]
108803367  ZBTB17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
108803590  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
108803625  [KO:K04501]
108803656  [KO:K11584]
108804551  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
108804600  DDX11; probable ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:3.6.4.13]
108804782  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
108805016  CCNB3; LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B3 [KO:K21771]
108805051  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
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
npr03030  DNA replication
npr04010  MAPK signaling pathway
npr04120  Ubiquitin mediated proteolysis
npr04210  Apoptosis
KO pathway
ko04110   

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