KEGG   PATHWAY: bta04110
Entry
bta04110                    Pathway                                
Name
Cell cycle - Bos taurus (cow)
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
bta04110  Cell cycle
bta04110

Other DBs
GO: 0000278
Organism
Bos taurus (cow) [GN:bta]
Gene
100134966  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
100138150  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X4 [KO:K03456]
100301478  CCNB3; G2/mitotic-specific cyclin-B3 isoform X2 [KO:K21771]
100336564  ANAPC2; anaphase-promoting complex subunit 2 isoform X1 [KO:K03349]
101905242  [KO:K25228]
112446327  [KO:K03347]
112446776  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
132342075  PTTG1; securin isoform X1 [KO:K06635]
132344360  [KO:K03456]
132345077  [KO:K05868]
281061  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
281302  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
281542  TP53; cellular tumor antigen p53 [KO:K04451]
281667  CCNA2; cyclin-A2 [KO:K06627]
281668  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
281729  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
282089  TGFB1; transforming growth factor beta-1 proprotein precursor [KO:K13375]
282125  YWHAE; 14-3-3 protein epsilon [KO:K06630]
282126  YWHAH; 14-3-3 protein eta [KO:K16198]
282320  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
282370  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
286862  YWHAG; 14-3-3 protein gamma [KO:K16198]
286863  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
287022  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
327679  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
337870  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
360192  AURKB; aurora kinase B [KO:K11479] [EC:2.7.11.1]
404126  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
407223  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
407228  CUL1; cullin-1 [KO:K03347]
504367  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
504869  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
504939  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
505356  ANAPC15; anaphase-promoting complex subunit 15 [KO:K25228]
505453  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
505463  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
505691  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
505757  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform [KO:K11584]
505847  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
505915  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
506293  DDX11; ATP-dependent DNA helicase DDX11 isoform X3 [KO:K11273] [EC:5.6.2.7]
506605  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
506740  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
506746  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
506970  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
507122  CDC45; cell division control protein 45 homolog [KO:K06628]
507731  CDC25C; M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
508043  PTTG1; securin [KO:K06635]
510120  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
510244  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
510618  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
510916  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
510972  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
511077  MYC; myc proto-oncogene protein [KO:K04377]
511281  ORC2; origin recognition complex subunit 2 [KO:K02604]
511754  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
512613  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
512651  CDC23; cell division cycle protein 23 homolog [KO:K03355]
512740  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
512915  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
513497  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
513523  ORC1; origin recognition complex subunit 1 [KO:K02603]
513678  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
514473  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
514572  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
514777  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
515080  FBXO5; F-box only protein 5 [KO:K10292]
515125  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
515301  CDC6; cell division control protein 6 homolog [KO:K02213]
515376  CDC20; cell division cycle protein 20 homolog [KO:K03363]
515462  CDK7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
515476  ORC6; origin recognition complex subunit 6 [KO:K02608]
515499  PCNA; proliferating cell nuclear antigen [KO:K04802]
516010  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
516094  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
517812  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
517837  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
518880  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
518897  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
519016  CDT1; DNA replication factor Cdt1 [KO:K10727]
519018  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
519217  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
519409  ORC5; origin recognition complex subunit 5 [KO:K02607]
520049  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
520188  CDC25A; M-phase inducer phosphatase 1 [KO:K06645] [EC:3.1.3.48]
520428  CDC14B; dual specificity protein phosphatase CDC14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
521939  CCNA1; cyclin-A1 [KO:K06627]
522122  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
522613  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
523714  ORC3; origin recognition complex subunit 3 [KO:K02605]
524361  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
524530  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
524870  RBL1; retinoblastoma-like protein 1 [KO:K04681]
524925  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
525428  E2F4; transcription factor E2F4 [KO:K04682]
526824  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
527124  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
528175  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
528453  SFN; 14-3-3 protein sigma [KO:K06644]
529245  ORC4; origin recognition complex subunit 4 [KO:K02606]
529868  TICRR; treslin [KO:K26117]
530333  FZR1; fizzy-related protein homolog [KO:K03364]
533206  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X2 [KO:K11267]
533294  RBL2; retinoblastoma-like protein 2 [KO:K16332]
533526  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
533617  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
533788  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
533890  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
534069  TGFB2; transforming growth factor beta-2 proprotein precursor [KO:K13376]
534322  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
534579  TFDP1; transcription factor Dp-1 [KO:K04683]
534712  RB1; retinoblastoma-associated protein [KO:K06618]
535035  ESCO1; N-acetyltransferase ESCO1 isoform X2 [KO:K11268] [EC:2.3.1.-]
535072  ANAPC7; anaphase-promoting complex subunit 7 [KO:K03354]
535321  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
535369  E2F1; transcription factor E2F1 [KO:K17454]
535565  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
537027  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
538238  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
538436  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
538789  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
538949  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
538957  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
539234  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
539427  E2F5; transcription factor E2F5 isoform X2 [KO:K04682]
539566  NIPBL; nipped-B-like protein [KO:K06672]
539594  BUB3; mitotic checkpoint protein BUB3 [KO:K02180]
539924  MCM7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
540089  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
540248  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
540322  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
540378  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
540537  ANAPC5; anaphase-promoting complex subunit 5 [KO:K03352]
540547  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
540660  CDC27; cell division cycle protein 27 homolog [KO:K03350]
540666  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
540876  ABL1; tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
540966  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
541184  E2F3; transcription factor E2F3 [KO:K06620]
613318  CDCA5; sororin [KO:K17390]
614056  SGO1; shugoshin 1 [KO:K11580]
614342  CDC16; cell division cycle protein 16 homolog [KO:K03353]
614347  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
614777  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
615016  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
615414  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
615427  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
615512  CCNH; cyclin-H [KO:K06634]
615542  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
616275  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
616369  CDKN2A; cyclin-dependent kinase inhibitor 2A isoform X2 [KO:K06621]
616487  STAG2; cohesin subunit SA-2 isoform 1 [KO:K06671]
616695  [KO:K03456]
617024  E2F2; transcription factor E2F2 isoform X2 [KO:K09389]
617904  MTBP; mdm2-binding protein [KO:K26116]
618405  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
768311  YWHAQ; 14-3-3 protein theta [KO:K16197]
777693  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
780968  [KO:K03868] [EC:2.3.2.32]
783986  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
785617  [KO:K03875]
786089  [KO:K11268] [EC:2.3.1.-]
787969  KNL1; LOW QUALITY PROTEIN: kinetochore scaffold 1 [KO:K11542]
790875  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
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
bta03030  DNA replication
bta04010  MAPK signaling pathway
bta04120  Ubiquitin mediated proteolysis
bta04210  Apoptosis
KO pathway
ko04110   

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