KEGG   PATHWAY: achc04110
Entry
achc04110                   Pathway                                
Name
Cell cycle - Aquila chrysaetos chrysaetos (golden eagle)
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
achc04110  Cell cycle
achc04110

Other DBs
GO: 0000278
Organism
Aquila chrysaetos chrysaetos (golden eagle) [GN:achc]
Gene
115333381  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
115333583  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
115333595  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
115333671  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
115333842  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
115334013  CDC23; cell division cycle protein 23 homolog isoform X1 [KO:K03355]
115334090  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
115334091  SKP1; S-phase kinase-associated protein 1 isoform X1 [KO:K03094]
115334106  PTTG1; securin [KO:K06635]
115334475  [KO:K06671]
115334634  CDC16; cell division cycle protein 16 homolog [KO:K03353]
115334656  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
115334941  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
115335097  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
115335151  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
115335243  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
115335296  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
115335353  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
115335526  [KO:K04498] [EC:2.3.1.48]
115335880  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
115335929  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
115336119  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
115336342  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
115336426  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
115336489  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
115336502  CCNH; cyclin-H isoform X2 [KO:K06634]
115336664  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
115336821  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
115336844  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
115336928  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
115336932  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
115337045  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
115337409  [KO:K04685]
115337410  [KO:K04685]
115337438  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
115337444  CCNA2; cyclin-A2 [KO:K06627]
115337560  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
115338264  TP53; LOW QUALITY PROTEIN: cellular tumor antigen p53 [KO:K04451]
115338351  MCM7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
115338925  CDC25B; M-phase inducer phosphatase 2 isoform X2 [KO:K05866] [EC:3.1.3.48]
115338979  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
115339020  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
115339047  SGO1; shugoshin 1 [KO:K11580]
115339219  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
115339343  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
115339346  CUL1; cullin-1 [KO:K03347]
115339384  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
115339525  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
115339886  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
115340040  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
115340093  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
115340094  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
115340115  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
115340182  NDC80; kinetochore protein NDC80 homolog isoform X1 [KO:K11547]
115340277  [KO:K26116]
115340295  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
115340375  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
115340445  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
115340697  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
115340741  MYC; LOW QUALITY PROTEIN: myc proto-oncogene protein [KO:K04377]
115341635  TICRR; LOW QUALITY PROTEIN: treslin [KO:K26117]
115341832  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
115341856  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
115341944  ORC5; origin recognition complex subunit 5 isoform X1 [KO:K02607]
115342595  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
115342898  MAD2L2; LOW QUALITY PROTEIN: mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
115342963  ORC2; origin recognition complex subunit 2 isoform X3 [KO:K02604]
115343205  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
115343211  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
115344107  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
115344343  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
115344491  FBXO5; F-box only protein 5 [KO:K10292]
115344524  CDC6; LOW QUALITY PROTEIN: cell division control protein 6 homolog [KO:K02213]
115344734  ANAPC1; anaphase-promoting complex subunit 1 isoform X3 [KO:K03348]
115344753  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
115344758  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
115344766  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
115344800  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
115345130  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X2 [KO:K11267]
115345300  [KO:K04501]
115345346  CDT1; DNA replication factor Cdt1 isoform X1 [KO:K10727]
115345410  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
115345421  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
115345430  CDC45; cell division control protein 45 homolog [KO:K06628]
115345995  YWHAH; 14-3-3 protein eta [KO:K16198]
115346208  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
115346339  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
115346404  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
115346591  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
115346635  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
115346661  ORC6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
115346776  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
115346823  YWHAG; 14-3-3 protein gamma [KO:K16198]
115346949  STAG1; cohesin subunit SA-1 isoform X3 [KO:K06671]
115347029  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
115347694  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
115347725  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
115348004  ANAPC16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
115348162  SMC3; structural maintenance of chromosomes protein 3 isoform X1 [KO:K06669]
115348234  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
115348394  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
115348462  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
115348766  CDC14A; LOW QUALITY PROTEIN: dual specificity protein phosphatase CDC14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
115348869  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
115349091  FZR1; fizzy-related protein homolog isoform X2 [KO:K03364]
115349100  CDC20; cell division cycle protein 20 homolog isoform X2 [KO:K03363]
115349520  CDC7; cell division cycle 7-related protein kinase isoform X3 [KO:K02214] [EC:2.7.11.1]
115349539  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
115349578  MAU2; MAU2 chromatid cohesion factor homolog [KO:K11266]
115349650  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
115349666  ORC1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
115350007  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
115350152  PCNA; proliferating cell nuclear antigen [KO:K04802]
115350245  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
115350306  TGFB2; transforming growth factor beta-2 proprotein [KO:K13376]
115350319  [KO:K26093]
115350525  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
115350578  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
115350880  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
115350895  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
115351030  YWHAQ; 14-3-3 protein theta [KO:K16197]
115351248  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
115351313  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
115351471  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
115351476  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
115351540  WEE1; wee1-like protein kinase isoform X2 [KO:K06632] [EC:2.7.11.1]
115351805  SFN; LOW QUALITY PROTEIN: 14-3-3 protein sigma [KO:K06644]
115351999  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
115352031  E2F2; LOW QUALITY PROTEIN: transcription factor E2F2 [KO:K09389]
115352058  KNL1; kinetochore scaffold 1 [KO:K11542]
115352206  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
115352277  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:3.6.4.13]
115352282  WEE2; wee1-like protein kinase 2 isoform X1 [KO:K06632] [EC:2.7.11.1]
115352320  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
115352350  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
115352414  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
115352528  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
115352685  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
115352780  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
115352787  [KO:K06625]
115352790  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
115352843  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
115352932  TRIP13; pachytene checkpoint protein 2 homolog isoform X3 [KO:K22399]
115353048  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
115353268  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
115353317  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
115353525  ANAPC15; anaphase-promoting complex subunit 15 [KO:K25228]
115353580  CCNA1; cyclin-A1 [KO:K06627]
121232389  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
121233000  [KO:K06672]
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
achc03030  DNA replication
achc04010  MAPK signaling pathway
achc04120  Ubiquitin mediated proteolysis
achc04210  Apoptosis
KO pathway
ko04110   

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