KEGG   PATHWAY: clv04110
Entry
clv04110                    Pathway                                
Name
Cell cycle - Columba livia (rock pigeon)
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
clv04110  Cell cycle
clv04110

Other DBs
GO: 0000278
Organism
Columba livia (rock pigeon) [GN:clv]
Gene
102083445  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
102083762  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102084273  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
102084508  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
102084553  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
102084576  RB1; retinoblastoma-associated protein [KO:K06618]
102084928  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
102084967  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
102085000  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
102085083  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
102085196  TGFB2; transforming growth factor beta-2 [KO:K13376]
102085264  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X2 [KO:K06643] [EC:2.3.2.27]
102085353  [KO:K04382] [EC:3.1.3.16]
102085398  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
102085406  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
102085414  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
102085548  CDC14A; LOW QUALITY PROTEIN: dual specificity protein phosphatase CDC14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102085604  ANAPC5; anaphase-promoting complex subunit 5 [KO:K03352]
102085722  [KO:K10779]
102085837  CDC45; cell division control protein 45 homolog [KO:K06628]
102085885  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
102085910  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
102085948  MYC; myc proto-oncogene protein [KO:K04377]
102085982  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
102086207  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
102086245  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102086381  ORC1; origin recognition complex subunit 1 [KO:K02603]
102086478  PCNA; proliferating cell nuclear antigen [KO:K04802]
102086623  E2F4; transcription factor E2F4 [KO:K04682]
102086631  [KO:K11479] [EC:2.7.11.1]
102086692  ANAPC16; LOW QUALITY PROTEIN: anaphase-promoting complex subunit 16 [KO:K25229]
102086741  ABL1; LOW QUALITY PROTEIN: tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
102086913  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
102087221  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
102087349  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
102087487  CDC25B; LOW QUALITY PROTEIN: M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
102087532  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102087534  KNL1; LOW QUALITY PROTEIN: kinetochore scaffold 1 [KO:K11542]
102087591  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
102088123  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
102088125  TGFB3; transforming growth factor beta-3 [KO:K13377]
102088146  [KO:K11479] [EC:2.7.11.1]
102088410  CCNH; cyclin-H [KO:K06634]
102088526  HDAC8; histone deacetylase 8 isoform X2 [KO:K11405] [EC:3.5.1.98]
102088592  [KO:K03456]
102088594  ORC5; origin recognition complex subunit 5 isoform X3 [KO:K02607]
102088637  DBF4B; protein DBF4 homolog B [KO:K06629]
102088821  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
102088851  ANAPC7; anaphase-promoting complex subunit 7 [KO:K03354]
102088890  CCNB3; G2/mitotic-specific cyclin-B3 isoform X2 [KO:K21771]
102089108  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
102089140  CCNA1; cyclin-A1 [KO:K06627]
102089360  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
102089372  PLK1; LOW QUALITY PROTEIN: serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
102089376  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
102089475  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
102089573  MCM6; LOW QUALITY PROTEIN: DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
102089676  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X4 [KO:K06679]
102089870  E2F3; transcription factor E2F3 isoform X3 [KO:K06620]
102090065  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102090072  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
102090134  CCND3; LOW QUALITY PROTEIN: G1/S-specific cyclin-D3 [KO:K10152]
102090450  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
102090639  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
102090710  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
102090722  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X2 [KO:K11584]
102090751  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
102090799  ATRX; transcriptional regulator ATRX [KO:K10779]
102090805  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
102090823  DDX11; LOW QUALITY PROTEIN: ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:3.6.4.13]
102090893  GSK3B; glycogen synthase kinase-3 beta isoform X3 [KO:K03083] [EC:2.7.11.26]
102090955  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
102091025  CDT1; DNA replication factor Cdt1 [KO:K10727]
102091159  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
102091219  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
102091343  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
102091430  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102091514  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
102091803  SGO1; shugoshin 1 [KO:K11580]
102092168  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
102092213  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
102092237  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
102092520  E2F5; transcription factor E2F5 [KO:K04682]
102092525  CDC20; cell division cycle protein 20 homolog [KO:K03363]
102092548  MTBP; mdm2-binding protein [KO:K26116]
102092778  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
102092950  CDC16; cell division cycle protein 16 homolog [KO:K03353]
102093196  CCND2; G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
102093247  STAG1; cohesin subunit SA-1 isoform X2 [KO:K06671]
102093444  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
102093465  FZR1; fizzy-related protein homolog [KO:K03364]
102093561  TICRR; treslin [KO:K26117]
102093567  MAU2; MAU2 chromatid cohesion factor homolog [KO:K11266]
102093584  CUL1; cullin-1 [KO:K03347]
102093629  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
102093777  ESCO1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
102093920  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102094005  CCNA2; cyclin-A2 [KO:K06627]
102094112  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
102094428  CHEK1; LOW QUALITY PROTEIN: serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
102094628  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
102094765  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
102094778  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
102094830  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
102094947  E2F2; transcription factor E2F2 [KO:K09389]
102094988  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
102095020  SMAD4; LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 4 [KO:K04501]
102095451  ORC6; origin recognition complex subunit 6 [KO:K02608]
102095468  SMAD3; LOW QUALITY PROTEIN: mothers against decapentaplegic homolog 3 [KO:K23605]
102095608  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
102095755  [KO:K06671]
102095842  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X2 [KO:K03868] [EC:2.3.2.32]
102095895  FBXO5; F-box only protein 5 [KO:K10292]
102095987  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
102096003  YWHAH; 14-3-3 protein eta [KO:K16198]
102096063  YWHAG; 14-3-3 protein gamma [KO:K16198]
102096090  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
102096269  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
102096384  TRIP13; pachytene checkpoint protein 2 homolog isoform X1 [KO:K22399]
102096538  E2F1; LOW QUALITY PROTEIN: transcription factor E2F1 [KO:K17454]
102096648  CDC6; cell division control protein 6 homolog [KO:K02213]
102096759  CDC23; cell division cycle protein 23 homolog [KO:K03355]
102096820  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102096870  WAPL; wings apart-like protein homolog isoform X2 [KO:K25163]
102097033  ANAPC15; anaphase-promoting complex subunit 15 [KO:K25228]
102097232  [KO:K04498] [EC:2.3.1.48]
102097340  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
102097597  ZBTB17; LOW QUALITY PROTEIN: zinc finger and BTB domain-containing protein 17 [KO:K10500]
102097780  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
102097806  SFN; 14-3-3 protein sigma [KO:K06644]
102097920  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
102097940  CDK7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
102098298  CCNB1; LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B1 [KO:K05868]
102098328  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
102098352  YWHAQ; 14-3-3 protein theta [KO:K16197]
102098392  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
102098411  RBL2; LOW QUALITY PROTEIN: retinoblastoma-like protein 2 [KO:K16332]
102098654  PTTG1; securin [KO:K06635]
102098866  [KO:K02212] [EC:5.6.2.3]
102098874  ORC4; origin recognition complex subunit 4 [KO:K02606]
102098899  CDC14B; dual specificity protein phosphatase CDC14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102099053  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [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.
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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.
  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
clv03030  DNA replication
clv04010  MAPK signaling pathway
clv04120  Ubiquitin mediated proteolysis
clv04210  Apoptosis
KO pathway
ko04110   

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