KEGG   PATHWAY: dsp04110
Entry
dsp04110                    Pathway                                
Name
Cell cycle - Dipodomys spectabilis (banner-tailed kangaroo rat)
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
dsp04110  Cell cycle
dsp04110

Other DBs
GO: 0000278
Organism
Dipodomys spectabilis (banner-tailed kangaroo rat) [GN:dsp]
Gene
122095112  Cdc14b; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
122095263  Atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
122095268  Tfdp2; transcription factor Dp-2 isoform X1 [KO:K09392]
122095677  Cdc25a; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
122095908  Cdc45; cell division control protein 45 homolog isoform X1 [KO:K06628]
122095937  Ywhah; 14-3-3 protein eta [KO:K16198]
122096425  Orc2; origin recognition complex subunit 2 [KO:K02604]
122096720  E2f5; transcription factor E2F5 isoform X1 [KO:K04682]
122096813  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
122096844  Orc6; origin recognition complex subunit 6 [KO:K02608]
122097162  Chek2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
122097410  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
122097446  Ccne1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
122097659  Atrx; transcriptional regulator ATRX isoform X1 [KO:K10779]
122098534  Anapc7; anaphase-promoting complex subunit 7 [KO:K03354]
122098584  Anapc5; LOW QUALITY PROTEIN: anaphase-promoting complex subunit 5 [KO:K03352]
122099165  Zbtb17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
122099301  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
122099415  Anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
122099860  Stag1; cohesin subunit SA-1 isoform X1 [KO:K06671]
122099882  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
122100012  Ticrr; treslin [KO:K26117]
122100133  Ywhae; 14-3-3 protein epsilon [KO:K06630]
122100140  [KO:K03351]
122100406  Aurkb; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
122100440  Tp53; cellular tumor antigen p53 [KO:K04451]
122100776  Ttk; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
122100822  Mau2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
122101247  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
122101347  Anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
122101491  Ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
122101503  Ccnd3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
122101560  [KO:K26093]
122101581  Mcm3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
122101637  Cdc27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
122102042  Cdc6; cell division control protein 6 homolog [KO:K02213]
122102080  Cdkn1c; cyclin-dependent kinase inhibitor 1C [KO:K09993]
122102140  [KO:K10151]
122102156  Smc1b; structural maintenance of chromosomes protein 1B [KO:K06636]
122102319  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
122102320  Rad21; double-strand-break repair protein rad21 homolog [KO:K06670]
122102408  Myc; myc proto-oncogene protein [KO:K04377]
122102469  [KO:K26116]
122102479  Ywhaz; 14-3-3 protein zeta/delta [KO:K16197]
122102516  Mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
122102531  Ddx11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:3.6.4.13]
122102556  Anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
122102663  [KO:K11580]
122103320  Dbf4b; protein DBF4 homolog B [KO:K06629]
122104082  Anapc4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
122104226  Chek1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
122104270  Smad2; mothers against decapentaplegic homolog 2 [KO:K04500]
122104287  Esco1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
122104309  Smad4; mothers against decapentaplegic homolog 4 [KO:K04501]
122104319  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
122104369  Ndc80; kinetochore protein NDC80 homolog [KO:K11547]
122104663  Ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
122105015  [KO:K17390]
122105635  Orc1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
122105784  Wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
122105888  Cul1; cullin-1 [KO:K03347]
122106167  [KO:K05868]
122106206  Cdc20; cell division cycle protein 20 homolog [KO:K03363]
122106294  [KO:K04382] [EC:3.1.3.16]
122106295  [KO:K04382] [EC:3.1.3.16]
122106643  Pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
122107009  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
122107720  Orc3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
122108031  Sgo1; shugoshin 1 [KO:K11580]
122108775  Ywhaq; 14-3-3 protein theta [KO:K16197]
122108952  Abl1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
122109317  Cdc14a; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
122109414  Ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
122109464  Tgfb2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
122109561  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
122109945  [KO:K06632] [EC:2.7.11.1]
122109981  Stag2; cohesin subunit SA-2 isoform X1 [KO:K06671]
122110009  Ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
122110174  Cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
122110260  Atm; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
122110283  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
122110597  [KO:K08866] [EC:2.7.12.1]
122110678  [KO:K03456]
122110812  Mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
122110853  Orc4; origin recognition complex subunit 4 [KO:K02606]
122110859  Cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
122111380  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
122111819  Dbf4; protein DBF4 homolog A [KO:K06629]
122111839  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
122111942  Orc5; origin recognition complex subunit 5 [KO:K02607]
122112009  Smc1a; structural maintenance of chromosomes protein 1A [KO:K06636]
122112130  Fbxo5; F-box only protein 5 [KO:K10292]
122112531  Pds5b; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
122112677  [KO:K03094]
122112773  Ccna1; cyclin-A1 [KO:K06627]
122112815  Rb1; retinoblastoma-associated protein [KO:K06618]
122113064  Prkdc; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
122113191  Mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
122113579  Mcm7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
122113593  Ywhag; 14-3-3 protein gamma [KO:K16198]
122113654  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
122113853  Mad1l1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
122114345  Anapc15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
122114453  Bub1b; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
122114469  Knl1; kinetochore scaffold 1 isoform X1 [KO:K11542]
122114500  Ccnb2; G2/mitotic-specific cyclin-B2 [KO:K21770]
122114693  Smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
122115181  E2f2; transcription factor E2F2 isoform X1 [KO:K09389]
122115255  Sfn; 14-3-3 protein sigma [KO:K06644]
122115382  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
122115441  Skp1; S-phase kinase-associated protein 1 [KO:K03094]
122115744  Smc3; structural maintenance of chromosomes protein 3 [KO:K06669]
122116188  Plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
122116275  Rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
122116471  Wapl; wings apart-like protein homolog isoform X1 [KO:K25163]
122116531  Anapc16; anaphase-promoting complex subunit 16 [KO:K25229]
122116982  Nipbl; nipped-B-like protein isoform X1 [KO:K06672]
122117008  Skp2; S-phase kinase-associated protein 2 [KO:K03875]
122117245  Ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
122117314  Cdk7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
122117316  Ccnh; cyclin-H [KO:K06634]
122117749  [KO:K03359]
122117819  Wee1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
122118117  Cdc23; cell division cycle protein 23 homolog isoform X1 [KO:K03355]
122118179  Cdc25c; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
122118877  Tgfb3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
122118978  Cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
122118979  [KO:K06621]
122119058  Mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
122119061  Ccna2; cyclin-A2 [KO:K06627]
122119229  Mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
122119810  Cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
122119814  Fzr1; fizzy-related protein homolog [KO:K03364]
122120195  Ywhab; 14-3-3 protein beta/alpha [KO:K16197]
122120249  Rbl1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
122120257  Pcna; proliferating cell nuclear antigen [KO:K04802]
122120305  E2f1; transcription factor E2F1 isoform X1 [KO:K17454]
122120345  Cdc25b; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
122120682  [KO:K11405] [EC:3.5.1.98]
122120962  Trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
122121039  Ccnb3; G2/mitotic-specific cyclin-B3 [KO:K21771]
122121346  [KO:K02178] [EC:2.7.11.1]
122121349  Bub1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
122121381  Anapc1; anaphase-promoting complex subunit 1 [KO:K03348]
122121412  Mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
122121563  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
122122286  Cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
122122369  Cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
122122586  Ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
122122679  Tfdp1; transcription factor Dp-1 isoform X1 [KO:K04683]
122122797  Cdc16; cell division cycle protein 16 homolog [KO:K03353]
122123350  [KO:K02216] [EC:2.7.11.1]
122123493  Esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
122123534  Ep300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
122123619  Rbx1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
122123684  [KO:K04498] [EC:2.3.1.48]
122123840  Pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
122124078  Mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
122124085  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
122124210  Espl1; separin [KO:K02365] [EC:3.4.22.49]
122124349  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
122125023  Pttg1; securin [KO:K06635]
122125515  [KO:K03456]
122125518  [KO:K03456]
122125535  [KO:K03456]
122125543  [KO:K03456]
122125547  [KO:K03456]
122126204  E2f4; transcription factor E2F4 [KO:K04682]
122126846  Bub3; mitotic checkpoint protein BUB3 [KO:K02180]
122126971  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
122127137  Anapc10; anaphase-promoting complex subunit 10 [KO:K03357]
122127949  Cdt1; DNA replication factor Cdt1 [KO:K10727]
122128263  [KO:K03351]
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
dsp03030  DNA replication
dsp04010  MAPK signaling pathway
dsp04120  Ubiquitin mediated proteolysis
dsp04210  Apoptosis
KO pathway
ko04110   

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