KEGG   PATHWAY: tup04110
Entry
tup04110                    Pathway                                
Name
Cell cycle - Tupaia chinensis (Chinese tree shrew)
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
tup04110  Cell cycle
tup04110

Other DBs
GO: 0000278
Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
102467782  ANAPC10; anaphase promoting complex subunit 10 [KO:K03357]
102468100  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
102468175  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
102468317  CCNE1; cyclin E1 [KO:K06626]
102468362  FZR1; fizzy/cell division cycle 20 related 1 [KO:K03364]
102468410  NDC80; NDC80, kinetochore complex component [KO:K11547]
102468598  RBX1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
102468641  TRIP13; thyroid hormone receptor interactor 13 [KO:K22399]
102468800  SFN; stratifin [KO:K06644]
102468840  ANAPC2; anaphase promoting complex subunit 2 [KO:K03349]
102469170  ORC6; origin recognition complex subunit 6 [KO:K02608]
102469333  ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
102469373  [KO:K03359]
102469774  ANAPC1; anaphase promoting complex subunit 1 [KO:K03348]
102469871  CDT1; chromatin licensing and DNA replication factor 1 [KO:K10727]
102469874  MAD2L1; MAD2 mitotic arrest deficient-like 1 (yeast) [KO:K02537]
102470554  ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
102471457  CDC14B; cell division cycle 14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102471617  TFDP1; transcription factor Dp-1 [KO:K04683]
102471654  YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
102472056  BUB3; BUB3, mitotic checkpoint protein [KO:K02180]
102472695  [KO:K21771]
102473158  SMAD3; SMAD family member 3 [KO:K23605]
102473395  PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584]
102473924  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
102474077  CDC25B; cell division cycle 25B [KO:K05866] [EC:3.1.3.48]
102474602  CDC16; cell division cycle 16 [KO:K03353]
102474804  ANAPC13; anaphase promoting complex subunit 13 [KO:K12456]
102475396  CCNA2; cyclin A2 [KO:K06627]
102475523  MAD1L1; MAD1 mitotic arrest deficient like 1 [KO:K06679]
102475690  [KO:K06635]
102475731  TTK; TTK protein kinase [KO:K08866] [EC:2.7.12.1]
102476038  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
102476190  CDCA5; cell division cycle associated 5 [KO:K17390]
102476408  CDC27; cell division cycle 27 [KO:K03350]
102476523  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
102476641  MCM2; minichromosome maintenance complex component 2 [KO:K02540] [EC:5.6.2.3]
102476721  RBL2; RB transcriptional corepressor like 2 [KO:K16332]
102476816  ORC3; origin recognition complex subunit 3 [KO:K02605]
102477051  MCM6; minichromosome maintenance complex component 6 [KO:K02542] [EC:5.6.2.3]
102477439  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
102477864  MAD2L1BP; MAD2L1 binding protein [KO:K26093]
102479161  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
102479178  ESCO2; establishment of sister chromatid cohesion N-acetyltransferase 2 [KO:K11268] [EC:2.3.1.-]
102479669  E2F2; E2F transcription factor 2 [KO:K09389]
102479902  CCND2; cyclin D2 [KO:K10151]
102480336  CDC26; cell division cycle 26 [KO:K03359]
102480650  MAD2L2; MAD2 mitotic arrest deficient-like 2 (yeast) [KO:K13728]
102480757  CHEK1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
102480852  CDC20; cell division cycle 20 [KO:K03363]
102480902  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
102481163  CDK7; cyclin dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
102481524  PCNA; proliferating cell nuclear antigen [KO:K04802]
102481951  WAPL; WAPL cohesin release factor [KO:K25163]
102481989  CCNB1; cyclin B1 [KO:K05868]
102482195  ATR; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
102482369  CDC25A; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
102482701  DBF4; DBF4 zinc finger [KO:K06629]
102482921  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
102482985  E2F4; E2F transcription factor 4 [KO:K04682]
102483469  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
102483646  SKP1; S-phase kinase associated protein 1 [KO:K03094]
102484147  CDKN2C; cyclin dependent kinase inhibitor 2C [KO:K06622]
102484272  TFDP2; transcription factor Dp-2 [KO:K09392]
102484800  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
102484832  E2F1; E2F transcription factor 1 [KO:K17454]
102484908  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
102484993  CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
102485345  MCM5; minichromosome maintenance complex component 5 [KO:K02209] [EC:5.6.2.3]
102485966  RBL1; RB transcriptional corepressor like 1 [KO:K04681]
102486561  CCNB3; cyclin B3 [KO:K21771]
102487526  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
102487950  [KO:K04382] [EC:3.1.3.16]
102488182  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
102488241  MCM7; minichromosome maintenance complex component 7 [KO:K02210] [EC:5.6.2.3]
102488319  KNL1; kinetochore scaffold 1 [KO:K11542]
102488432  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102488524  TGFB1; transforming growth factor beta 1 [KO:K13375]
102488550  PDS5A; PDS5 cohesin associated factor A [KO:K11267]
102488678  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
102489182  ANAPC11; anaphase promoting complex subunit 11 [KO:K03358]
102489231  AURKB; aurora kinase B [KO:K11479] [EC:2.7.11.1]
102489331  CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102489382  SMC1A; structural maintenance of chromosomes 1A [KO:K06636]
102489527  DBF4B; DBF4 zinc finger B [KO:K06629]
102489720  CDKN2D; cyclin dependent kinase inhibitor 2D [KO:K06623]
102489925  CCNA1; cyclin A1 [KO:K06627]
102490133  ZBTB17; zinc finger and BTB domain containing 17 [KO:K10500]
102490159  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
102490203  CDC14A; cell division cycle 14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102490246  MTBP; MDM2 binding protein [KO:K26116]
102490545  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
102490651  CCND1; cyclin D1 [KO:K04503]
102490834  WEE2; WEE1 homolog 2 [KO:K06632] [EC:2.7.11.1]
102491175  TICRR; TOPBP1 interacting checkpoint and replication regulator [KO:K26117]
102491766  RAD21; RAD21 cohesin complex component [KO:K06670]
102491982  ANAPC5; anaphase promoting complex subunit 5 [KO:K03352]
102492088  CCNE2; cyclin E2 [KO:K06626]
102492609  CDC7; cell division cycle 7 [KO:K02214] [EC:2.7.11.1]
102492839  CCNH; cyclin H [KO:K06634]
102492990  ORC2; origin recognition complex subunit 2 [KO:K02604]
102493291  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102493420  MCM3; minichromosome maintenance complex component 3 [KO:K02541] [EC:5.6.2.3]
102493697  NIPBL; NIPBL, cohesin loading factor [KO:K06672]
102493876  BUB1B; BUB1 mitotic checkpoint serine/threonine kinase B [KO:K06637] [EC:2.7.11.1]
102494008  SMAD4; SMAD family member 4 [KO:K04501]
102494667  FBXO5; F-box protein 5 [KO:K10292]
102494746  PLK1; polo like kinase 1 [KO:K06631] [EC:2.7.11.21]
102494755  ORC1; origin recognition complex subunit 1 [KO:K02603]
102495017  PTTG1; pituitary tumor-transforming 1 [KO:K06635]
102495776  DDX11; DEAD/H-box helicase 11 [KO:K11273] [EC:3.6.4.13]
102495782  PDS5B; PDS5 cohesin associated factor B [KO:K11267]
102495801  [KO:K04685]
102495890  CDC23; cell division cycle 23 [KO:K03355]
102496029  SMC3; structural maintenance of chromosomes 3 [KO:K06669]
102496402  CDC45; cell division cycle 45 [KO:K06628]
102496436  ANAPC16; anaphase promoting complex subunit 16 [KO:K25229]
102496583  MCM4; minichromosome maintenance complex component 4 [KO:K02212] [EC:5.6.2.3]
102496861  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
102496957  ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
102497029  TGFB3; transforming growth factor beta 3 [KO:K13377]
102497164  SKP2; S-phase kinase associated protein 2 [KO:K03875]
102497222  MAU2; MAU2 sister chromatid cohesion factor [KO:K11266]
102497296  PRKDC; protein kinase, DNA-activated, catalytic polypeptide [KO:K06642] [EC:2.7.11.1]
102497318  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
102497446  CUL1; cullin 1 [KO:K03347]
102497985  CDC6; cell division cycle 6 [KO:K02213]
102498008  [KO:K02202] [EC:2.7.11.22 2.7.11.23]
102498533  ORC4; origin recognition complex subunit 4 [KO:K02606]
102498805  BUB1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
102498926  ESPL1; extra spindle pole bodies like 1, separase [KO:K02365] [EC:3.4.22.49]
102498982  [KO:K05868]
102499060  CDC25C; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
102499416  E2F3; E2F transcription factor 3 [KO:K06620]
102499491  YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
102499507  RB1; RB transcriptional corepressor 1 [KO:K06618]
102499541  SMAD2; SMAD family member 2 [KO:K04500]
102499577  CCND3; cyclin D3 [KO:K10152]
102499593  STAG2; stromal antigen 2 [KO:K06671]
102500015  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
102500173  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
102500294  CDKN2B; cyclin dependent kinase inhibitor 2B [KO:K04685]
102500295  ESCO1; establishment of sister chromatid cohesion N-acetyltransferase 1 [KO:K11268] [EC:2.3.1.-]
102500482  TGFB2; transforming growth factor beta 2 [KO:K13376]
102500616  STAG1; stromal antigen 1 [KO:K06671]
102500626  ANAPC15; anaphase promoting complex subunit 15 [KO:K25228]
102500800  WEE1; WEE1 G2 checkpoint kinase [KO:K06632] [EC:2.7.11.1]
102500872  E2F5; E2F transcription factor 5 [KO:K04682]
102500901  CDKN1C; cyclin dependent kinase inhibitor 1C [KO:K09993]
102501209  PKMYT1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
102501231  ATRX; ATRX, chromatin remodeler [KO:K10779]
102501235  CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624]
102501273  SGO1; shugoshin 1 [KO:K11580]
102501319  CCNB2; cyclin B2 [KO:K21770]
102501582  ORC5; origin recognition complex subunit 5 [KO:K02607]
102501999  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
102502093  ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
102502647  SMC1B; structural maintenance of chromosomes 1B [KO:K06636]
102502813  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
102503025  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
102503238  TP53; tumor protein p53 [KO:K04451]
102503291  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
Reference
PMID:7908906
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Matsuoka S, Yamaguchi M, Matsukage A
  Title
D-type cyclin-binding regions of proliferating cell nuclear antigen.
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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)
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Reference
PMID:16936746
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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.
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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?
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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.
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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.
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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.
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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
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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.
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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)
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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
tup03030  DNA replication
tup04010  MAPK signaling pathway
tup04120  Ubiquitin mediated proteolysis
tup04210  Apoptosis
KO pathway
ko04110   

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