KEGG   PATHWAY: mjv04110
Entry
mjv04110                    Pathway                                
Name
Cell cycle - Manis javanica (Malayan pangolin)
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
mjv04110  Cell cycle
mjv04110

Other DBs
GO: 0000278
Organism
Manis javanica (Malayan pangolin) [GN:mjv]
Gene
108383293  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
108383431  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
108383560  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
108383720  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
108384360  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
108384449  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
108384606  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
108384777  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
108384899  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
108385057  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
108385232  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
108385295  CDC25C; M-phase inducer phosphatase 3 isoform X2 [KO:K05867] [EC:3.1.3.48]
108385726  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B isoform X1 [KO:K13728]
108385913  [KO:K06625]
108386438  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
108386600  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
108386649  [KO:K02537]
108386652  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
108386656  CUL1; cullin-1 [KO:K03347]
108387110  WEE1; wee1-like protein kinase isoform X2 [KO:K06632] [EC:2.7.11.1]
108387122  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
108387305  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
108387401  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
108387425  ANAPC10; anaphase-promoting complex subunit 10 isoform X4 [KO:K03357]
108387631  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
108388060  WAPL; wings apart-like protein homolog [KO:K25163]
108388183  BUB1; LOW QUALITY PROTEIN: mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
108388302  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
108388312  WEE2; wee1-like protein kinase 2 isoform X1 [KO:K06632] [EC:2.7.11.1]
108388354  RBL2; retinoblastoma-like protein 2 [KO:K16332]
108388480  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
108389003  GSK3B; glycogen synthase kinase-3 beta isoform X5 [KO:K03083] [EC:2.7.11.26]
108389723  [KO:K06635]
108389738  PPP2R5C; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform [KO:K11584]
108390143  CDC27; cell division cycle protein 27 homolog isoform X7 [KO:K03350]
108390313  E2F4; transcription factor E2F4 isoform X2 [KO:K04682]
108390373  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
108390553  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
108390572  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
108390866  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
108391234  ORC5; origin recognition complex subunit 5 [KO:K02607]
108391598  CDC7; cell division cycle 7-related protein kinase isoform X2 [KO:K02214] [EC:2.7.11.1]
108391616  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
108391654  TICRR; treslin [KO:K26117]
108391758  ANAPC16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
108391911  ORC4; origin recognition complex subunit 4 isoform X2 [KO:K02606]
108392032  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
108392194  CDC6; cell division control protein 6 homolog [KO:K02213]
108392535  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
108393260  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
108393274  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
108393303  YWHAG; 14-3-3 protein gamma [KO:K16198]
108393837  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
108394195  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
108394315  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
108394317  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
108394324  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
108394338  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
108394362  KNL1; kinetochore scaffold 1 isoform X1 [KO:K11542]
108394400  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
108394445  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
108394455  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
108394467  [KO:K16198]
108394490  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
108394496  CCNH; cyclin-H isoform X1 [KO:K06634]
108394547  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
108394726  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
108395051  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X2 [KO:K11584]
108395237  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
108395362  [KO:K04498] [EC:2.3.1.48]
108395538  RAD21; double-strand-break repair protein rad21 homolog isoform X1 [KO:K06670]
108395671  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
108395918  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
108396147  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
108396377  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X2 [KO:K11584]
108396385  [KO:K17390]
108396431  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
108397427  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
108397838  SFN; 14-3-3 protein sigma [KO:K06644]
108397991  [KO:K04682]
108398257  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
108398307  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
108398376  PCNA; proliferating cell nuclear antigen [KO:K04802]
108398611  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
108398654  YWHAQ; 14-3-3 protein theta [KO:K16197]
108399491  NDC80; kinetochore protein NDC80 homolog isoform X1 [KO:K11547]
108399966  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
108399968  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
108399996  MYC; myc proto-oncogene protein [KO:K04377]
108400099  CCNA2; cyclin-A2 isoform X2 [KO:K06627]
108400532  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
108400540  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
108400736  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
108401047  CHEK1; serine/threonine-protein kinase Chk1 isoform X2 [KO:K02216] [EC:2.7.11.1]
108401113  E2F1; transcription factor E2F1 [KO:K17454]
108401143  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
108401353  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
108401564  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
108401579  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
108401648  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
108401870  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
108402112  ORC6; origin recognition complex subunit 6 isoform X2 [KO:K02608]
108402211  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
108402565  [KO:K11584]
108402658  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
108402686  PTTG1; securin isoform X2 [KO:K06635]
108403151  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
108403423  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
108403582  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
108403673  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
108403976  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
108403997  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
108404206  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
108404266  TP53; cellular tumor antigen p53 [KO:K04451]
108404270  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
108404446  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
108404582  DDX11; ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:3.6.4.13]
108404608  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
108404720  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
108404778  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
108404799  CCNA1; cyclin-A1 isoform X1 [KO:K06627]
108404801  STAG1; cohesin subunit SA-1 [KO:K06671]
108404892  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
108405092  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
108405335  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
108405366  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
108405368  ESPL1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
108405702  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X2 [KO:K03456]
108405977  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
108405988  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
108406080  [KO:K04382] [EC:3.1.3.16]
108406083  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
108406875  CDC45; cell division control protein 45 homolog [KO:K06628]
108406891  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
108407024  CDC20; cell division cycle protein 20 homolog [KO:K03363]
108407128  [KO:K26093]
108407530  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
108407680  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
108407870  SMC1A; structural maintenance of chromosomes protein 1A isoform X2 [KO:K06636]
108408026  ANAPC4; anaphase-promoting complex subunit 4 [KO:K03351]
108408195  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
108408272  ORC1; LOW QUALITY PROTEIN: origin recognition complex subunit 1 [KO:K02603]
108408453  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
108408615  TRIP13; pachytene checkpoint protein 2 homolog isoform X1 [KO:K22399]
108408683  CDKN1C; cyclin-dependent kinase inhibitor 1C isoform X1 [KO:K09993]
108408718  [KO:K26116]
108409500  CDC25B; M-phase inducer phosphatase 2 isoform X2 [KO:K05866] [EC:3.1.3.48]
108409537  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
108409674  FBXO5; F-box only protein 5 [KO:K10292]
108409680  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
108409726  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
108409857  SGO1; shugoshin 1 isoform X1 [KO:K11580]
108410323  CDC23; cell division cycle protein 23 homolog [KO:K03355]
108410330  [KO:K06671]
118967462  [KO:K16198]
118968813  [KO:K02537]
118969876  [KO:K03357]
118970122  [KO:K06625]
118971891  [KO:K11268] [EC:2.3.1.-]
118972014  [KO:K04382] [EC:3.1.3.16]
118972255  [KO:K05866] [EC:3.1.3.48]
118972765  [KO:K06621]
118974052  [KO:K04451]
Reference
PMID:7908906
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  Title
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J Biol Chem 269:11030-6 (1994)
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Reference
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Oncogene 25:5263-7 (2006)
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Reference
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Oncogene 24:2796-809 (2005)
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Reference
PMID:17568790
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  Title
CDC25 phosphatases in cancer cells: key players? Good targets?
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Nat Rev Cancer 7:495-507 (2007)
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Reference
PMID:9832503
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Genes Dev 12:3499-511 (1998)
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Reference
PMID:19020303
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Transcriptional regulation of the cyclin D1 gene at a glance.
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J Cell Sci 121:3853-7 (2008)
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Reference
PMID:10385618
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CDK inhibitors: positive and negative regulators of G1-phase progression.
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Genes Dev 13:1501-12 (1999)
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Reference
PMID:12809600
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Mechanisms of TGF-beta signaling from cell membrane to the nucleus.
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Cell 113:685-700 (2003)
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PMID:12925736
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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.
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Proc Natl Acad Sci U S A 100:10231-6 (2003)
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Reference
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  Authors
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Biphasic effect of p21Cip1 on smooth muscle cell proliferation: role of PI 3-kinase and Skp2-mediated degradation.
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Cardiovasc Res 69:198-206 (2006)
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Reference
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The p53 pathway: positive and negative feedback loops.
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Oncogene 24:2899-908 (2005)
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Reference
PMID:11099028
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Surfing the p53 network.
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Nature 408:307-10 (2000)
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Reference
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Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression.
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Mol Cell 24:101-13 (2006)
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Reference
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Reference
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Reference
PMID:17426725
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Reference
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Reference
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Reference
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  Title
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Reference
PMID:20935501
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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
mjv03030  DNA replication
mjv04010  MAPK signaling pathway
mjv04120  Ubiquitin mediated proteolysis
mjv04210  Apoptosis
KO pathway
ko04110   

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