KEGG   PATHWAY: iti04110
Entry
iti04110                    Pathway                                
Name
Cell cycle - Ictidomys tridecemlineatus (thirteen-lined ground 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
iti04110  Cell cycle
iti04110

Other DBs
GO: 0000278
Organism
Ictidomys tridecemlineatus (thirteen-lined ground squirrel) [GN:iti]
Gene
101954402  E2f4; transcription factor E2F4 isoform X1 [KO:K04682]
101954599  Ywhah; 14-3-3 protein eta isoform X2 [KO:K16198]
101954723  Plk1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
101954960  [KO:K26093]
101955392  Ywhae; 14-3-3 protein epsilon isoform X1 [KO:K06630]
101955441  Mad2l2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
101955790  [KO:K16197]
101956260  Mcm5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
101956303  Cdt1; DNA replication factor Cdt1 [KO:K10727]
101956515  Orc2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
101956610  Ccnb3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
101956748  Ywhab; 14-3-3 protein beta/alpha [KO:K16197]
101956838  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
101956926  Abl1; tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
101957026  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101957086  Myc; myc proto-oncogene protein [KO:K04377]
101957126  Rbx1; E3 ubiquitin-protein ligase RBX1 isoform X2 [KO:K03868] [EC:2.3.2.32]
101957179  Mcm6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
101957181  Bub1b; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X2 [KO:K06637] [EC:2.7.11.1]
101957244  Wee1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
101957396  Orc5; origin recognition complex subunit 5 isoform X1 [KO:K02607]
101957629  Mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
101957648  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
101957668  [KO:K04498] [EC:2.3.1.48]
101957738  Tp53; cellular tumor antigen p53 [KO:K04451]
101957951  Sfn; 14-3-3 protein sigma [KO:K06644]
101958117  Ccne1; G1/S-specific cyclin-E1 isoform X2 [KO:K06626]
101958129  Cdc45; cell division control protein 45 homolog isoform X1 [KO:K06628]
101958348  Pkmyt1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
101958365  Pcna; proliferating cell nuclear antigen [KO:K04802]
101958546  Ppp2cb; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101959195  Orc6; origin recognition complex subunit 6 [KO:K02608]
101959564  Esco2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
101959923  Rbl1; retinoblastoma-like protein 1 [KO:K04681]
101959977  Bub3; mitotic checkpoint protein BUB3 isoform X4 [KO:K02180]
101960142  Tfdp1; transcription factor Dp-1 isoform X1 [KO:K04683]
101960195  Cdc25c; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
101960248  Cdk7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
101960323  Mad2l1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
101960584  Esco1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
101960650  Cdc16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
101960742  Pds5a; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
101960804  Chek2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
101961033  Trip13; pachytene checkpoint protein 2 homolog [KO:K22399]
101961145  Nipbl; nipped-B-like protein isoform X1 [KO:K06672]
101961313  Ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
101961577  Ccnh; cyclin-H isoform X1 [KO:K06634]
101961671  Mcm3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
101961685  Anapc1; anaphase-promoting complex subunit 1 [KO:K03348]
101961791  Tgfb3; transforming growth factor beta-3 proprotein [KO:K13377]
101961877  Cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
101961922  E2f1; transcription factor E2F1 [KO:K17454]
101962193  Cdc23; cell division cycle protein 23 homolog [KO:K03355]
101962278  Smad4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
101962416  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101962418  Cdc25a; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
101962445  Ppp2r5d; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X2 [KO:K11584]
101962490  Atm; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
101962771  Cdc26; anaphase-promoting complex subunit CDC26 [KO:K03359]
101962778  Mcm4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
101963061  Prkdc; DNA-dependent protein kinase catalytic subunit isoform X3 [KO:K06642] [EC:2.7.11.1]
101963242  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
101963424  Anapc7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
101963921  Ppp2r5a; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
101963954  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
101964194  Cdc27; cell division cycle protein 27 homolog isoform X3 [KO:K03350]
101964196  Ywhag; 14-3-3 protein gamma [KO:K16198]
101964207  Anapc11; anaphase-promoting complex subunit 11 [KO:K03358]
101964394  Dbf4b; protein DBF4 homolog B isoform X1 [KO:K06629]
101964905  Zbtb17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
101964971  Aurkb; aurora kinase B isoform X3 [KO:K11479] [EC:2.7.11.1]
101965246  [KO:K16197]
101965468  Cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
101965526  Anapc15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
101965902  Mcm2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
101965959  Cdkn2d; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
101966226  Orc3; origin recognition complex subunit 3 isoform X4 [KO:K02605]
101966364  Pds5b; sister chromatid cohesion protein PDS5 homolog B isoform X2 [KO:K11267]
101966556  Atrx; transcriptional regulator ATRX isoform X3 [KO:K10779]
101966841  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
101966934  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
101966960  Anapc4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
101967025  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
101967027  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X4 [KO:K03456]
101967037  Ccna2; cyclin-A2 [KO:K06627]
101967116  Fzr1; fizzy-related protein homolog isoform X1 [KO:K03364]
101967226  Skp1; S-phase kinase-associated protein 1 isoform X1 [KO:K03094]
101967492  [KO:K03094]
101967599  Tgfb2; transforming growth factor beta-2 proprotein isoform X2 [KO:K13376]
101967961  Cdc7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
101968071  Smc1b; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
101968080  [KO:K26116]
101968120  Smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
101968271  Ywhaz; 14-3-3 protein zeta/delta [KO:K16197]
101968394  Chek1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
101968397  Hdac8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
101968536  Cul1; cullin-1 [KO:K03347]
101968565  Ndc80; kinetochore protein NDC80 homolog [KO:K11547]
101968576  Rbl2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
101968588  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
101969116  Ywhaq; 14-3-3 protein theta [KO:K16197]
101969262  Cdkn1c; cyclin-dependent kinase inhibitor 1C [KO:K09993]
101969266  Cdc25b; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
101969267  Cdc14b; dual specificity protein phosphatase CDC14B isoform X11 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101969390  Orc1; origin recognition complex subunit 1 [KO:K02603]
101969912  Sgo1; shugoshin 1 isoform X1 [KO:K11580]
101969946  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
101969993  Tgfb1; transforming growth factor beta-1 proprotein [KO:K13375]
101970019  Smc1a; structural maintenance of chromosomes protein 1A isoform X4 [KO:K06636]
101970285  [KO:K03868] [EC:2.3.2.32]
101970300  Ccnd3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
101970757  [KO:K26093]
101970887  Ticrr; treslin isoform X2 [KO:K26117]
101971034  Mcm7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
101971676  [KO:K06643] [EC:2.3.2.27]
101972246  Ccna1; cyclin-A1 [KO:K06627]
101972403  Wee2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
101972535  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101972609  Cdkn2b; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101972847  Ppp2r5e; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X4 [KO:K11584]
101972899  Ccnb2; G2/mitotic-specific cyclin-B2 [KO:K21770]
101973092  Rad21; double-strand-break repair protein rad21 homolog [KO:K06670]
101973097  Smad3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
101973588  Stag2; cohesin subunit SA-2 isoform X1 [KO:K06671]
101973820  Anapc13; anaphase-promoting complex subunit 13 [KO:K12456]
101974177  Cdc6; cell division control protein 6 homolog [KO:K02213]
101974624  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101974627  Wapl; wings apart-like protein homolog isoform X1 [KO:K25163]
101974796  [KO:K21770]
101975128  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
101975155  Orc4; origin recognition complex subunit 4 [KO:K02606]
101975322  Tfdp2; transcription factor Dp-2 isoform X1 [KO:K09392]
101975521  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
101975569  Smc3; LOW QUALITY PROTEIN: structural maintenance of chromosomes protein 3 [KO:K06669]
101975622  Cdca5; sororin isoform X2 [KO:K17390]
101975689  Skp2; S-phase kinase-associated protein 2 isoform X4 [KO:K03875]
101975692  Cdkn2c; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
101975699  E2f5; transcription factor E2F5 isoform X1 [KO:K04682]
101975748  Ppp2r5c; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
101975776  Anapc16; anaphase-promoting complex subunit 16 [KO:K25229]
101975815  Anapc2; anaphase-promoting complex subunit 2 [KO:K03349]
101976066  Rb1; retinoblastoma-associated protein isoform X3 [KO:K06618]
101976118  Dbf4; protein DBF4 homolog A [KO:K06629]
101976364  Mau2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
101976448  Stag1; cohesin subunit SA-1 isoform X1 [KO:K06671]
101976540  Ttk; dual specificity protein kinase TTK isoform X3 [KO:K08866] [EC:2.7.12.1]
101976552  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101976911  Atr; serine/threonine-protein kinase ATR isoform X4 [KO:K06640] [EC:2.7.11.1]
101977070  [KO:K06635]
101977127  [KO:K06621]
101977546  Espl1; separin [KO:K02365] [EC:3.4.22.49]
101977585  Ppp2r5b; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
101977746  Anapc10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
101977754  Anapc5; anaphase-promoting complex subunit 5 [KO:K03352]
101977768  Cdk4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
101978133  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
101978145  Knl1; kinetochore scaffold 1 [KO:K11542]
101978178  Fbxo5; F-box only protein 5 [KO:K10292]
101978417  Ddx11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
101978440  Cdc20; cell division cycle protein 20 homolog [KO:K03363]
101978637  E2f2; transcription factor E2F2 [KO:K09389]
120889971  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
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
iti03030  DNA replication
iti04010  MAPK signaling pathway
iti04120  Ubiquitin mediated proteolysis
iti04210  Apoptosis
KO pathway
ko04110   

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