KEGG   PATHWAY: cdk04110
Entry
cdk04110                    Pathway                                
Name
Cell cycle - Camelus dromedarius (Arabian camel)
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
cdk04110  Cell cycle
cdk04110

Other DBs
GO: 0000278
Organism
Camelus dromedarius (Arabian camel) [GN:cdk]
Gene
105104393  CCND1; LOW QUALITY PROTEIN: G1/S-specific cyclin-D1 [KO:K04503]
105091327  CCND2; LOW QUALITY PROTEIN: G1/S-specific cyclin-D2 [KO:K10151]
105086756  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
105100330  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
105088747  CDK6; cyclin-dependent kinase 6 isoform X2 [KO:K02091] [EC:2.7.11.22]
105101803  RB1; LOW QUALITY PROTEIN: retinoblastoma-associated protein [KO:K06618]
105085041  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
105097515  RBL2; retinoblastoma-like protein 2 [KO:K16332]
105092528  ABL1; tyrosine-protein kinase ABL1 isoform X4 [KO:K06619] [EC:2.7.10.2]
105085792  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
105099222  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
105092697  E2F1; LOW QUALITY PROTEIN: transcription factor E2F1 [KO:K17454]
105088895  E2F2; transcription factor E2F2 [KO:K09389]
105089193  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105088486  E2F4; transcription factor E2F4 [KO:K04682]
105088507  E2F5; LOW QUALITY PROTEIN: transcription factor E2F5 [KO:K04682]
105091346  TFDP1; transcription factor Dp-1 [KO:K04683]
105086325  TFDP2; transcription factor Dp-2 isoform X3 [KO:K09392]
105090321  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105093367  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
105100091  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
105086078  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
105097587  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
105093274  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
105103392  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
105096445  MYC; myc proto-oncogene protein [KO:K04377]
105107114  ZBTB17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
105092872  cyclin-dependent kinase inhibitor 2A-like isoform X1 [KO:K06621]
105092868  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
105092949  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
105087685  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
105094245  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
105104556  LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 1C [KO:K09993]
105101330  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
105085741  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
105096784  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
105086385  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
105090262  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
105085195  CUL1; cullin-1 [KO:K03347]
105091911  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
105086996  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
105093659  CCNA2; cyclin-A2 [KO:K06627]
105100862  CCNA1; cyclin-A1 [KO:K06627]
105099022  CDC6; cell division control protein 6 homolog isoform X1 [KO:K02213]
105104701  CDT1; LOW QUALITY PROTEIN: DNA replication factor Cdt1 [KO:K10727]
105092965  ORC1; origin recognition complex subunit 1 [KO:K02603]
105099176  ORC2; origin recognition complex subunit 2 [KO:K02604]
105095544  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
105084610  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
105093020  ORC5; origin recognition complex subunit 5 isoform X1 [KO:K02607]
105091179  ORC6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
105090108  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
105099527  MCM3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
105095922  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
105097387  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
105092298  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
105104801  MCM7; DNA replication licensing factor MCM7 isoform X2 [KO:K02210] [EC:5.6.2.3]
105095244  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
105094670  TICRR; treslin [KO:K26117]
105098319  MTBP; mdm2-binding protein [KO:K26116]
105085464  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
105087361  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
105094420  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
105093852  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
105084760  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
105088978  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
105090090  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
105096018  CDC25B; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
105090655  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
105087105  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
105091237  YWHAQ; 14-3-3 protein theta [KO:K16197]
105090535  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
105088124  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
105099415  YWHAH; 14-3-3 protein eta [KO:K16198]
105089727  YWHAG; 14-3-3 protein gamma [KO:K16198]
105086861  LOW QUALITY PROTEIN: 14-3-3 protein eta-like [KO:K16198]
105094832  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
105093996  WEE1; LOW QUALITY PROTEIN: wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
105097323  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
105099691  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
105099633  CCNH; cyclin-H isoform X1 [KO:K06634]
105084765  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
105093737  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
105106182  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
105090429  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
105098371  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
105102507  ANAPC5; anaphase-promoting complex subunit 5 [KO:K03352]
105095492  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
105102495  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
105090638  CDC23; cell division cycle protein 23 homolog [KO:K03355]
105091213  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
105106389  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
116152716  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
105085287  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
105096682  ANAPC15; anaphase-promoting complex subunit 15 isoform X2 [KO:K25228]
105092484  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
105090909  CDC20; cell division cycle protein 20 homolog [KO:K03363]
105099911  PTTG1; securin isoform X1 [KO:K06635]
105094570  ESPL1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
105091845  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
105096694  SMC1A; structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
105091704  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
105096150  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
105085279  STAG1; cohesin subunit SA-1 [KO:K06671]
105098885  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
105095566  ATRX; transcriptional regulator ATRX isoform X4 [KO:K10779]
105102958  DDX11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
105086991  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
105103734  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
105098583  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
105086296  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
105102188  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
105089333  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X2 [KO:K11267]
105100964  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
105096588  WAPL; LOW QUALITY PROTEIN: wings apart-like protein homolog [KO:K25163]
105102619  sororin [KO:K17390]
105102991  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
105085151  SGO1; shugoshin 1 [KO:K11580]
105090279  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
105095814  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
105094015  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
105092005  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
105088611  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
105086205  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
105102628  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
105105619  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
105099311  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
105086121  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
105096878  KNL1; kinetochore scaffold 1 [KO:K11542]
105103948  TTK; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
105104789  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
105093650  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
105107030  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
105096887  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
105085759  BUB3; mitotic checkpoint protein BUB3 isoform X4 [KO:K02180]
105092966  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
105102181  TRIP13; pachytene checkpoint protein 2 homolog isoform X1 [KO:K22399]
105088630  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
105102657  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
105100930  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
105084682  CDC14B; LOW QUALITY PROTEIN: dual specificity protein phosphatase CDC14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
105084951  CDC14A; dual specificity protein phosphatase CDC14A isoform X5 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
105091909  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
105099829  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
105095924  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
105086328  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
105096603  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
105101086  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
105103011  TP53; cellular tumor antigen p53 [KO:K04451]
105086406  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105103609  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105096626  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
105101416  PCNA; proliferating cell nuclear antigen [KO:K04802]
105100696  SFN; 14-3-3 protein sigma [KO:K06644]
105094454  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
105099476  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
105103857  CDC25A; 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.
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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.
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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
cdk03030  DNA replication
cdk04010  MAPK signaling pathway
cdk04120  Ubiquitin mediated proteolysis
cdk04210  Apoptosis
KO pathway
ko04110   
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