KEGG   PATHWAY: aju04110
Entry
aju04110                    Pathway                                
Name
Cell cycle - Acinonyx jubatus (cheetah)
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
aju04110  Cell cycle
aju04110

Other DBs
GO: 0000278
Organism
Acinonyx jubatus (cheetah) [GN:aju]
Gene
106971167  G1/S-specific cyclin-D1 [KO:K04503]
106965383  G1/S-specific cyclin-D2 [KO:K10151]
106974052  G1/S-specific cyclin-D3 isoform X2 [KO:K10152]
106975871  cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
106969949  cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
106971960  retinoblastoma-associated protein isoform X1 [KO:K06618]
106979285  retinoblastoma-like protein 1 isoform X1 [KO:K04681]
106984720  retinoblastoma-like protein 2 isoform X1 [KO:K16332]
106985340  tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
106968918  histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
106982428  histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
106974609  transcription factor E2F1 isoform X2 [KO:K17454]
106977597  transcription factor E2F2 [KO:K09389]
106987605  transcription factor E2F3 isoform X3 [KO:K06620]
106971492  transcription factor E2F4 [KO:K04682]
106982308  transcription factor E2F5 isoform X1 [KO:K04682]
106986699  transcription factor Dp-1 isoform X1 [KO:K04683]
106981976  transcription factor Dp-2 isoform X4 [KO:K09392]
106968274  glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
106987682  transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
106979500  transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
106974351  transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
106972947  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
106980367  mothers against decapentaplegic homolog 3 isoform X3 [KO:K23605]
106974966  mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
106976895  myc proto-oncogene protein [KO:K04377]
106975602  zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
106986386  cyclin-dependent kinase inhibitor 2A-like [KO:K06621]
106986385  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
106973704  cyclin-dependent kinase 4 inhibitor C [KO:K06622]
106980320  cyclin-dependent kinase 4 inhibitor D [KO:K06623]
106965649  cyclin-dependent kinase inhibitor 1B [KO:K06624]
113595462  LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 1C [KO:K09993]
106972797  cyclin-dependent kinase inhibitor 1 [KO:K06625]
106974883  G1/S-specific cyclin-E2 [KO:K06626]
106975766  G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
106986916  cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
106984903  S-phase kinase-associated protein 1 [KO:K03094]
106981418  cullin-1 [KO:K03347]
113602716  E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
106979642  S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
106977098  cyclin-A2 [KO:K06627]
106973846  cyclin-A1 isoform X1 [KO:K06627]
106980562  cell division control protein 6 homolog isoform X1 [KO:K02213]
106973503  DNA replication factor Cdt1 [KO:K10727]
106986689  origin recognition complex subunit 1 isoform X1 [KO:K02603]
106987982  origin recognition complex subunit 2 isoform X2 [KO:K02604]
106972540  origin recognition complex subunit 3 isoform X1 [KO:K02605]
106971528  origin recognition complex subunit 4 isoform X1 [KO:K02606]
106979782  origin recognition complex subunit 5 isoform X1 [KO:K02607]
106965988  origin recognition complex subunit 6 isoform X1 [KO:K02608]
106985738  DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
106973060  DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
106982123  DNA replication licensing factor MCM4 isoform X2 [KO:K02212] [EC:5.6.2.3]
106981037  DNA replication licensing factor MCM5 isoform X1 [KO:K02209] [EC:5.6.2.3]
106969450  DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
106987422  DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
106983631  cell division control protein 45 homolog isoform X1 [KO:K06628]
106965924  treslin isoform X2 [KO:K26117]
106978181  mdm2-binding protein isoform X1 [KO:K26116]
106968063  cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
106987586  protein DBF4 homolog A isoform X1 [KO:K06629]
106988158  LOW QUALITY PROTEIN: protein DBF4 homolog B [KO:K06629]
106989884  cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
106977069  G2/mitotic-specific cyclin-B1 [KO:K05868]
106973791  G2/mitotic-specific cyclin-B2 isoform X2 [KO:K21770]
106975278  G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
106980182  M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
106967966  M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
106973494  LOW QUALITY PROTEIN: 14-3-3 protein zeta/delta-like [KO:K16197]
106968957  14-3-3 protein beta/alpha [KO:K16197]
106982949  14-3-3 protein theta [KO:K16197]
106989479  14-3-3 protein theta [KO:K16197]
106980045  14-3-3 protein zeta/delta [KO:K16197]
106981227  LOW QUALITY PROTEIN: 14-3-3 protein epsilon-like [KO:K06630]
106983214  14-3-3 protein epsilon isoform X2 [KO:K06630]
106983312  14-3-3 protein eta [KO:K16198]
106980702  14-3-3 protein gamma [KO:K16198]
106970495  serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
106979484  wee1-like protein kinase isoform X2 [KO:K06632] [EC:2.7.11.1]
106970444  wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
106978727  membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X2 [KO:K06633] [EC:2.7.11.1]
106978597  cyclin-H isoform X1 [KO:K06634]
106977073  cyclin-dependent kinase 7 isoform X8 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
106976028  anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
106989188  anaphase-promoting complex subunit 2 [KO:K03349]
106988840  cell division cycle protein 27 homolog isoform X1 [KO:K03350]
106975106  anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
106967544  anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
106986696  cell division cycle protein 16 homolog isoform X1 [KO:K03353]
106967588  anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
106968052  cell division cycle protein 23 homolog [KO:K03355]
106983767  anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
106986336  anaphase-promoting complex subunit 11 [KO:K03358]
106978358  anaphase-promoting complex subunit CDC26 isoform X1 [KO:K03359]
128312965  LOW QUALITY PROTEIN: anaphase-promoting complex subunit 13-like [KO:K12456]
106987464  anaphase-promoting complex subunit 13 [KO:K12456]
106970937  anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
106967175  anaphase-promoting complex subunit 16 [KO:K25229]
106970210  cell division cycle protein 20 homolog isoform X1 [KO:K03363]
106967609  securin isoform X1 [KO:K06635]
113596816  securin-like [KO:K06635]
106986457  separin [KO:K02365] [EC:3.4.22.49]
106967286  structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
106985383  structural maintenance of chromosomes protein 1A [KO:K06636]
106984754  structural maintenance of chromosomes protein 3 isoform X1 [KO:K06669]
106975538  double-strand-break repair protein rad21 homolog [KO:K06670]
106972833  cohesin subunit SA-2 isoform X1 [KO:K06671]
106982040  cohesin subunit SA-2-like isoform X1 [KO:K06671]
106976818  cohesin subunit SA-1 isoform X1 [KO:K06671]
106988441  transcriptional regulator ATRX isoform X1 [KO:K10779]
106965395  ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
106980340  nipped-B-like protein isoform X1 [KO:K06672]
106969066  MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
106982392  histone deacetylase 8 isoform X8 [KO:K11405] [EC:3.5.1.98]
106970033  N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
106973127  N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
106985073  sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
106973857  sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
106982653  wings apart-like protein homolog isoform X1 [KO:K25163]
106971152  sororin isoform X1 [KO:K17390]
106972512  aurora kinase B isoform X3 [KO:K11479] [EC:2.7.11.1]
106981652  shugoshin 1 [KO:K11580]
106966583  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
106984892  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
106984444  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
106973000  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
106966766  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
106975965  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X4 [KO:K11584]
106971318  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
106974042  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
106971234  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X2 [KO:K11584]
106986076  kinetochore protein NDC80 homolog isoform X1 [KO:K11547]
106968537  kinetochore scaffold 1 [KO:K11542]
106976575  dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
106984516  mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
106979581  mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
106971873  mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
106968546  mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
106969393  mitotic checkpoint protein BUB3 isoform X3 [KO:K02180]
106976032  mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
106989546  pachytene checkpoint protein 2 homolog isoform X1 [KO:K22399]
106974020  MAD2L1-binding protein isoform X1 [KO:K26093]
106982135  fizzy-related protein homolog isoform X1 [KO:K03364]
106976256  F-box only protein 5 isoform X1 [KO:K10292]
106976415  dual specificity protein phosphatase CDC14A isoform X2 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
106971486  dual specificity protein phosphatase CDC14B isoform X7 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
106979918  histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
106978741  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
106982122  DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
106982261  LOW QUALITY PROTEIN: serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
106983963  serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
106966348  E3 ubiquitin-protein ligase Mdm2 isoform X3 [KO:K06643] [EC:2.3.2.27]
106972437  cellular tumor antigen p53 [KO:K04451]
106989693  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
106985200  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
113594268  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
106980177  proliferating cell nuclear antigen [KO:K04802]
106977554  14-3-3 protein sigma [KO:K06644]
106976641  serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
106985461  serine/threonine-protein kinase Chk2 isoform X3 [KO:K06641] [EC:2.7.11.1]
106979176  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
aju03030  DNA replication
aju04010  MAPK signaling pathway
aju04120  Ubiquitin mediated proteolysis
aju04210  Apoptosis
KO pathway
ko04110   
LinkDB

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