KEGG   PATHWAY: ncar04110
Entry
ncar04110                   Pathway                                
Name
Cell cycle - Sciurus carolinensis (gray squirrel)
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
ncar04110  Cell cycle
ncar04110

Other DBs
GO: 0000278
Organism
Sciurus carolinensis (gray squirrel) [GN:ncar]
Gene
124958520  G1/S-specific cyclin-D1 [KO:K04503]
124982598  G1/S-specific cyclin-D2 [KO:K10151]
124988186  G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
124983907  cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
124990984  cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
124985088  retinoblastoma-associated protein isoform X1 [KO:K06618]
124976795  retinoblastoma-like protein 1 isoform X1 [KO:K04681]
124966292  LOW QUALITY PROTEIN: retinoblastoma-like protein 2 [KO:K16332]
124965033  tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
124988795  histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
124960595  histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
124977154  transcription factor E2F1 [KO:K17454]
124990231  transcription factor E2F2 [KO:K09389]
124988927  transcription factor E2F3 isoform X1 [KO:K06620]
124992777  LOW QUALITY PROTEIN: transcription factor E2F5-like [KO:K04682]
124994534  transcription factor E2F5 isoform X1 [KO:K04682]
124991484  transcription factor E2F5-like [KO:K04682]
124966525  transcription factor E2F4 [KO:K04682]
124985834  transcription factor Dp-1 [KO:K04683]
124992733  transcription factor Dp-2 isoform X1 [KO:K09392]
124992642  LOW QUALITY PROTEIN: glycogen synthase kinase-3 beta-like [KO:K03083] [EC:2.7.11.26]
124967085  transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
124962328  transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
124977343  transforming growth factor beta-3 proprotein [KO:K13377]
124965420  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
124973148  mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
124965442  mothers against decapentaplegic homolog 4 [KO:K04501]
124965808  myc proto-oncogene protein [KO:K04377]
124965249  zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
124964288  cyclin-dependent kinase inhibitor 2A-like isoform X1 [KO:K06621]
124964289  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
124988066  cyclin-dependent kinase 4 inhibitor C [KO:K06622]
124969363  cyclin-dependent kinase 4 inhibitor D [KO:K06623]
124983239  cyclin-dependent kinase inhibitor 1B [KO:K06624]
124960747  cyclin-dependent kinase inhibitor 1C-like isoform X1 [KO:K09993]
124989493  cyclin-dependent kinase inhibitor 1-like [KO:K06625]
124967069  G1/S-specific cyclin-E1 [KO:K06626]
124977262  G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
124982038  cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
124986638  S-phase kinase-associated protein 1 [KO:K03094]
124961935  S-phase kinase-associated protein 1 [KO:K03094]
124964174  S-phase kinase-associated protein 1-like [KO:K03094]
124971813  S-phase kinase-associated protein 1-like [KO:K03094]
124965809  S-phase kinase-associated protein 1-like [KO:K03094]
124990585  cullin-1 [KO:K03347]
124977175  LOW QUALITY PROTEIN: cullin-1-like [KO:K03347]
124983356  E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
124986905  S-phase kinase-associated protein 2 [KO:K03875]
124994687  LOW QUALITY PROTEIN: cyclin-A2-like [KO:K06627]
124985165  cyclin-A1 [KO:K06627]
124979932  cell division control protein 6 homolog [KO:K02213]
124966492  DNA replication factor Cdt1-like isoform X1 [KO:K10727]
124991029  origin recognition complex subunit 1-like [KO:K02603]
124980446  origin recognition complex subunit 2 [KO:K02604]
124988049  origin recognition complex subunit 3 isoform X1 [KO:K02605]
124981190  origin recognition complex subunit 4 isoform X1 [KO:K02606]
124991161  origin recognition complex subunit 5 [KO:K02607]
124987628  origin recognition complex subunit 6-like [KO:K02608]
124966788  origin recognition complex subunit 6-like [KO:K02608]
124971056  DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
124988597  DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
124987692  DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
124981860  DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
124981361  DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
124970189  DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
124990838  cell division control protein 45 homolog isoform X1 [KO:K06628]
124977172  treslin-like [KO:K26117]
124962308  mdm2-binding protein-like [KO:K26116]
124965295  cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
124990955  protein DBF4 homolog A-like isoform X1 [KO:K06629]
124980366  protein DBF4 homolog B-like isoform X1 [KO:K06629]
124984914  LOW QUALITY PROTEIN: cyclin-dependent kinase 1-like [KO:K02087] [EC:2.7.11.22 2.7.11.23]
124987022  G2/mitotic-specific cyclin-B1 [KO:K05868]
124970575  G2/mitotic-specific cyclin-B2 [KO:K21770]
124972154  G2/mitotic-specific cyclin-B3-like [KO:K21771]
124975972  M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
124987233  M-phase inducer phosphatase 3-like isoform X1 [KO:K05867] [EC:3.1.3.48]
124977026  14-3-3 protein theta-like [KO:K16197]
124977108  14-3-3 protein beta/alpha [KO:K16197]
124984929  14-3-3 protein zeta/delta [KO:K16197]
124963524  14-3-3 protein theta [KO:K16197]
124974529  LOW QUALITY PROTEIN: 14-3-3 protein beta/alpha-like [KO:K16197]
124974530  LOW QUALITY PROTEIN: 14-3-3 protein beta/alpha-like [KO:K16197]
124980358  14-3-3 protein epsilon isoform X1 [KO:K06630]
124991637  14-3-3 protein eta [KO:K16198]
124970548  14-3-3 protein gamma [KO:K16198]
124970412  serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
124990480  wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
124959823  wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
124970177  membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
124987004  cyclin-H [KO:K06634]
124987092  cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
124963058  anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
124964771  anaphase-promoting complex subunit 2 [KO:K03349]
124979876  cell division cycle protein 27 homolog isoform X1 [KO:K03350]
124994098  anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
124990690  anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
124984879  cell division cycle protein 16 homolog [KO:K03353]
124991612  anaphase-promoting complex subunit 7 [KO:K03354]
124994459  anaphase-promoting complex subunit 10 [KO:K03357]
124979693  anaphase-promoting complex subunit 11 [KO:K03358]
124964718  anaphase-promoting complex subunit CDC26 [KO:K03359]
124990583  anaphase-promoting complex subunit 13-like [KO:K12456]
124992568  anaphase-promoting complex subunit 13 [KO:K12456]
124958183  anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
124984352  anaphase-promoting complex subunit 16 [KO:K25229]
124983936  cell division cycle protein 20 homolog [KO:K03363]
124987197  securin-like [KO:K06635]
124989197  LOW QUALITY PROTEIN: securin-like [KO:K06635]
124983017  separin-like isoform X1 [KO:K02365] [EC:3.4.22.49]
124972559  structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
124982985  LOW QUALITY PROTEIN: structural maintenance of chromosomes protein 1B-like [KO:K06636]
124985105  structural maintenance of chromosomes protein 3 [KO:K06669]
124961737  double-strand-break repair protein rad21 homolog [KO:K06670]
124992572  cohesin subunit SA-1 isoform X1 [KO:K06671]
124971784  cohesin subunit SA-2 isoform X1 [KO:K06671]
124971398  LOW QUALITY PROTEIN: transcriptional regulator ATRX-like [KO:K10779]
124982000  putative ATP-dependent RNA helicase DDX11-like protein 8 isoform X1 [KO:K11273] [EC:5.6.2.7]
124987257  nipped-B-like protein isoform X1 [KO:K06672]
124968832  MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
124972184  histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
124965450  N-acetyltransferase ESCO1-like [KO:K11268] [EC:2.3.1.-]
124983228  N-acetyltransferase ESCO2-like isoform X1 [KO:K11268] [EC:2.3.1.-]
124994095  sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
124984856  LOW QUALITY PROTEIN: sister chromatid cohesion protein PDS5 homolog B-like [KO:K11267]
124984828  LOW QUALITY PROTEIN: wings apart-like protein homolog [KO:K25163]
124958436  uncharacterized protein LOC124958436 [KO:K17390]
124988132  LOW QUALITY PROTEIN: sororin-like [KO:K17390]
124958883  sororin-like [KO:K17390]
124980265  aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
124968789  shugoshin 1-like isoform X1 [KO:K11580]
124987135  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
124983945  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
124958287  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
124967003  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
124958310  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
124988657  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
124976854  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
124961576  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
124973978  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform-like [KO:K11584]
124976126  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
124965795  kinetochore protein NDC80 homolog [KO:K11547]
124977918  kinetochore scaffold 1-like [KO:K11542]
124988787  dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
124970253  mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
124994765  LOW QUALITY PROTEIN: mitotic spindle assembly checkpoint protein MAD2A-like [KO:K02537]
124994892  mitotic spindle assembly checkpoint protein MAD2A-like isoform X1 [KO:K02537]
124982415  mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
124976879  mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
124985510  mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
124963154  mitotic checkpoint serine/threonine-protein kinase BUB1-like [KO:K02178] [EC:2.7.11.1]
124986813  pachytene checkpoint protein 2 homolog [KO:K22399]
124988652  LOW QUALITY PROTEIN: MAD2L1-binding protein-like [KO:K26093]
124968461  fizzy-related protein homolog isoform X1 [KO:K03364]
124988684  F-box only protein 5-like isoform X1 [KO:K10292]
124990379  dual specificity protein phosphatase CDC14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
124965604  dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
124969981  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
124982357  histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
124981191  DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
124992921  serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
124958109  LOW QUALITY PROTEIN: serine-protein kinase ATM-like [KO:K04728] [EC:2.7.11.1]
124971738  E3 ubiquitin-protein ligase Mdm2-like [KO:K06643] [EC:2.3.2.27]
124983594  E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
124980281  cellular tumor antigen p53 [KO:K04451]
124987492  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
124968653  growth arrest and DNA damage-inducible protein GADD45 beta isoform X1 [KO:K04402]
124965544  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
124978151  proliferating cell nuclear antigen [KO:K04802]
124980974  14-3-3 protein sigma [KO:K06644]
124958320  serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
124991831  serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
124969415  M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
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
ncar03030  DNA replication
ncar04010  MAPK signaling pathway
ncar04120  Ubiquitin mediated proteolysis
ncar04210  Apoptosis
KO pathway
ko04110   
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