KEGG   PATHWAY: afz04110
Entry
afz04110                    Pathway                                
Name
Cell cycle - Antechinus flavipes (yellow-footed antechinus)
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
afz04110  Cell cycle
afz04110

Other DBs
GO: 0000278
Organism
Antechinus flavipes (yellow-footed antechinus) [GN:afz]
Gene
127539835  G1/S-specific cyclin-D1 [KO:K04503]
127539247  G1/S-specific cyclin-D2 [KO:K10151]
127561736  G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
127538222  cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
127537888  cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
127555178  retinoblastoma-associated protein isoform X1 [KO:K06618]
127550410  retinoblastoma-like protein 1 [KO:K04681]
127550708  retinoblastoma-like protein 2 isoform X1 [KO:K16332]
127550913  tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
127562109  histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
127555505  histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
127555063  histone deacetylase 2-like [KO:K06067] [EC:3.5.1.98]
127550324  transcription factor E2F1 [KO:K17454]
127555707  transcription factor E2F2 [KO:K09389]
127544127  transcription factor E2F3 [KO:K06620]
127543711  transcription factor E2F5 [KO:K04682]
127547919  transcription factor E2F4 isoform X1 [KO:K04682]
127553497  transcription factor Dp-1 isoform X1 [KO:K04683]
127552996  transcription factor Dp-2 isoform X1 [KO:K09392]
127554112  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
127556228  transforming growth factor beta-1 proprotein [KO:K13375]
127562518  transforming growth factor beta-2 proprotein [KO:K13376]
127549479  transforming growth factor beta-3 proprotein [KO:K13377]
127543521  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
127551234  mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
127543493  mothers against decapentaplegic homolog 4 [KO:K04501]
127544452  myc proto-oncogene protein [KO:K04377]
127555826  zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
127545332  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
127563336  cyclin-dependent kinase 4 inhibitor C [KO:K06622]
127544735  LOW QUALITY PROTEIN: cyclin-dependent kinase 4 inhibitor D [KO:K06623]
127539369  cyclin-dependent kinase inhibitor 1B [KO:K06624]
127542095  cyclin-dependent kinase inhibitor 1C [KO:K09993]
127561515  cyclin-dependent kinase inhibitor 1 [KO:K06625]
127550660  G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
127544298  G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
127564952  cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
127549826  S-phase kinase-associated protein 1 [KO:K03094]
127564895  cullin-1 [KO:K03347]
127539224  LOW QUALITY PROTEIN: cullin-1-like [KO:K03347]
127538369  E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
127556614  S-phase kinase-associated protein 2 [KO:K03875]
127541195  cyclin-A2 [KO:K06627]
127555246  cyclin-A1 isoform X1 [KO:K06627]
127560189  cell division control protein 6 homolog [KO:K02213]
127547787  DNA replication factor Cdt1 [KO:K10727]
127563318  origin recognition complex subunit 1 [KO:K02603]
127553234  origin recognition complex subunit 2 [KO:K02604]
127561981  origin recognition complex subunit 3 [KO:K02605]
127554383  origin recognition complex subunit 4 isoform X1 [KO:K02606]
127564066  origin recognition complex subunit 5 isoform X1 [KO:K02607]
127550672  origin recognition complex subunit 6 [KO:K02608]
127552893  DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
127561847  DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
127543890  DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
127538093  DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
127554358  DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
127560993  DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
127545727  cell division control protein 45 homolog [KO:K06628]
127551391  treslin [KO:K26117]
127544409  mdm2-binding protein [KO:K26116]
127563490  cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
127564409  protein DBF4 homolog A isoform X1 [KO:K06629]
127557750  protein DBF4 homolog A-like [KO:K06629]
127560352  protein DBF4 homolog B [KO:K06629]
127552134  cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
127558326  G2/mitotic-specific cyclin-B1 [KO:K05868]
127551202  G2/mitotic-specific cyclin-B2 [KO:K21770]
127547413  M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
127549958  M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
127548860  14-3-3 protein beta/alpha [KO:K16197]
127544337  14-3-3 protein zeta/delta [KO:K16197]
127548618  14-3-3 protein theta [KO:K16197]
127558846  14-3-3 protein epsilon isoform X1 [KO:K06630]
127558652  14-3-3 protein gamma [KO:K16198]
127545717  14-3-3 protein eta isoform X1 [KO:K16198]
127540148  serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
127564221  wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
127539628  LOW QUALITY PROTEIN: wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
127542570  membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
127559402  cyclin-H [KO:K06634]
127558341  cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
127548403  anaphase-promoting complex subunit 1 [KO:K03348]
127549077  anaphase-promoting complex subunit 2 [KO:K03349]
127560386  cell division cycle protein 27 homolog isoform X1 [KO:K03350]
127540921  anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
127545449  anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
127553505  cell division cycle protein 16 homolog [KO:K03353]
127545458  anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
127549954  LOW QUALITY PROTEIN: cell division cycle protein 23 homolog [KO:K03355]
127541193  anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
127560628  anaphase-promoting complex subunit 11 [KO:K03358]
127550806  anaphase-promoting complex subunit CDC26 [KO:K03359]
127554221  anaphase-promoting complex subunit 13 [KO:K12456]
127555258  anaphase-promoting complex subunit 15 [KO:K25228]
127551941  anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
127563462  cell division cycle protein 20 homolog isoform X1 [KO:K03363]
127554775  LOW QUALITY PROTEIN: cell division cycle protein 20 homolog [KO:K03363]
127550159  securin [KO:K06635]
127538318  separin isoform X1 [KO:K02365] [EC:3.4.22.49]
127538987  structural maintenance of chromosomes protein 1B [KO:K06636]
127539173  structural maintenance of chromosomes protein 1A [KO:K06636]
127551573  structural maintenance of chromosomes protein 3 [KO:K06669]
127544387  double-strand-break repair protein rad21 homolog [KO:K06670]
127543222  cohesin subunit SA-2 isoform X1 [KO:K06671]
127553697  cohesin subunit SA-2-like [KO:K06671]
127554229  cohesin subunit SA-1 [KO:K06671]
127542646  transcriptional regulator ATRX isoform X1 [KO:K10779]
127542761  LOW QUALITY PROTEIN: transcriptional regulator ATRX-like [KO:K10779]
127539340  ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
127556680  nipped-B-like protein isoform X1 [KO:K06672]
127544997  MAU2 chromatid cohesion factor homolog [KO:K11266]
127553288  histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
127548804  N-acetyltransferase ESCO2 isoform X1 [KO:K11268] [EC:2.3.1.-]
127543965  N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
127554682  sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
127540799  sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
127552027  wings apart-like protein homolog isoform X1 [KO:K25163]
127559021  aurora kinase B-like [KO:K11479] [EC:2.7.11.1]
127560843  aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
127564541  shugoshin 1 isoform X1 [KO:K11580]
127549824  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
127539590  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
127539655  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform-like [KO:K04382] [EC:3.1.3.16]
127556425  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
127554975  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
127562576  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
127549612  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
127549900  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
127540094  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
127561763  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
127543981  kinetochore protein NDC80 homolog [KO:K11547]
127546632  kinetochore scaffold 1-like [KO:K11542]
127561942  dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
127563986  mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
127540379  mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
127555873  mitotic spindle assembly checkpoint protein MAD2B isoform X1 [KO:K13728]
127549221  mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
127551670  mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
127548397  mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
127543584  pachytene checkpoint protein 2 homolog [KO:K22399]
127561790  MAD2L1-binding protein [KO:K26093]
127542528  fizzy-related protein homolog [KO:K03364]
127544983  fizzy-related protein homolog [KO:K03364]
127562342  F-box only protein 5 [KO:K10292]
127559453  dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
127561551  dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
127542170  CREB-binding protein [KO:K04498] [EC:2.3.1.48]
127538400  histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
127543891  DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
127552991  serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
127554958  serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
127564477  E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
127538796  E3 ubiquitin-protein ligase Mdm2-like [KO:K06643] [EC:2.3.2.27]
127560870  cellular tumor antigen p53 isoform X1 [KO:K04451]
127563174  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
127545137  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
127552133  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
127548185  proliferating cell nuclear antigen [KO:K04802]
127555643  14-3-3 protein sigma [KO:K06644]
127554847  serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
127545635  serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [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
afz03030  DNA replication
afz04010  MAPK signaling pathway
afz04120  Ubiquitin mediated proteolysis
afz04210  Apoptosis
KO pathway
ko04110   
LinkDB

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