KEGG   PATHWAY: phi04110
Entry
phi04110                    Pathway                                
Name
Cell cycle - Pseudopodoces humilis (Tibetan ground-tit)
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
phi04110  Cell cycle
phi04110

Other DBs
GO: 0000278
Organism
Pseudopodoces humilis (Tibetan ground-tit) [GN:phi]
Gene
102099659  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102114518  CCND2; G1/S-specific cyclin-D2 isoform X1 [KO:K10151]
102106455  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
102103942  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102114646  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102105165  RB1; retinoblastoma-associated protein [KO:K06618]
102103337  RBL1; retinoblastoma-like protein 1 isoform X3 [KO:K04681]
102106505  RBL2; retinoblastoma-like protein 2 [KO:K16332]
102099348  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
102104750  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
102102768  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
102114020  E2F1; transcription factor E2F1 [KO:K17454]
102101185  transcription factor E2F2 [KO:K09389]
102099157  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102101691  E2F5; transcription factor E2F5 [KO:K04682]
102108638  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
102111680  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
102109128  TFDP2; transcription factor Dp-2 isoform X2 [KO:K09392]
102105491  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
102112781  TGFB1; transforming growth factor beta-1 [KO:K13375]
102114598  TGFB2; transforming growth factor beta-2 [KO:K13376]
102102248  TGFB3; transforming growth factor beta-3 [KO:K13377]
102100805  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
102110827  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
102113882  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
102111851  mothers against decapentaplegic homolog 4-like [KO:K04501]
102108851  MYC; myc proto-oncogene protein [KO:K04377]
102106196  ZBTB17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
102111222  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
102111403  cyclin-dependent kinase 4 inhibitor B-like [KO:K04685]
102101327  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
102099407  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
102109596  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
102112135  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102111744  CCNE2; G1/S-specific cyclin-E2 isoform X2 [KO:K06626]
102114128  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
102108666  cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
102099878  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
102100590  CUL1; cullin-1 isoform X2 [KO:K03347]
102102832  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
102109076  SKP2; S-phase kinase-associated protein 2 isoform X3 [KO:K03875]
102112787  CCNA1; cyclin-A1 [KO:K06627]
102106141  CCNA2; cyclin-A2 isoform X1 [KO:K06627]
102112455  CDC6; cell division control protein 6 homolog [KO:K02213]
102109377  CDT1; DNA replication factor Cdt1 [KO:K10727]
102104153  ORC1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
102110957  ORC2; origin recognition complex subunit 2 [KO:K02604]
102103779  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
102112983  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
102108524  ORC5; origin recognition complex subunit 5 [KO:K02607]
102112437  ORC6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
102109954  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
102101288  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
102108308  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
102101786  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
102099872  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
102106593  MCM7; DNA replication licensing factor MCM7 [KO:K02210] [EC:5.6.2.3]
102101599  CDC45; cell division control protein 45 homolog [KO:K06628]
102102681  TICRR; treslin [KO:K26117]
102113542  MTBP; mdm2-binding protein [KO:K26116]
102106170  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
102111014  DBF4; protein DBF4 homolog A isoform X3 [KO:K06629]
102099783  DBF4B; protein DBF4 homolog B [KO:K06629]
102104995  CDK1; cyclin-dependent kinase 1 isoform X1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102109952  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
102112498  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
102106150  M-phase inducer phosphatase 2-like [KO:K05866] [EC:3.1.3.48]
102106234  YWHAQ; 14-3-3 protein theta [KO:K16197]
102106659  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
102106991  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
102101840  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
102099694  YWHAH; 14-3-3 protein eta [KO:K16198]
102109068  YWHAG; 14-3-3 protein gamma [KO:K16198]
102106048  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
102113696  WEE1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
102104410  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
102100097  CCNH; cyclin-H [KO:K06634]
102114195  CDK7; cyclin-dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
102107672  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
102106755  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
102113279  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
102111623  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
102113315  ANAPC5; anaphase-promoting complex subunit 5 [KO:K03352]
102110941  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
102112182  ANAPC7; anaphase-promoting complex subunit 7 [KO:K03354]
102106305  CDC23; cell division cycle protein 23 homolog isoform X1 [KO:K03355]
102114493  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
102105578  ANAPC11; anaphase-promoting complex subunit 11 isoform X1 [KO:K03358]
102110981  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
102111542  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
102104038  anaphase-promoting complex subunit 15-like [KO:K25228]
102105493  ANAPC15; anaphase-promoting complex subunit 15 [KO:K25228]
102112709  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
102103056  CDC20; cell division cycle protein 20 homolog [KO:K03363]
102111880  PTTG1; securin [KO:K06635]
102109021  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
102113008  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
102109155  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
102108740  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
102100337  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
102105498  RAD21L1; double-strand-break repair protein rad21-like protein 1 [KO:K06670]
102113412  cohesin subunit SA-2-like isoform X1 [KO:K06671]
102113888  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
102101735  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
102105378  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
102109321  DDX11; probable ATP-dependent RNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
102113764  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
102100637  MAU2; MAU2 chromatid cohesion factor homolog [KO:K11266]
102111947  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
102100463  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
106628437  N-acetyltransferase ESCO1-like [KO:K11268] [EC:2.3.1.-]
106628719  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
102110939  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X2 [KO:K11267]
102106414  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
102107104  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
102101749  aurora kinase B-like [KO:K11479] [EC:2.7.11.1]
102107220  SGOL1; shugoshin-like 1 [KO:K11580]
102100299  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102109205  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
102099118  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
102103370  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
102100781  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
102112538  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X2 [KO:K11584]
102108724  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X3 [KO:K11584]
102102478  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
102100037  kinetochore protein NDC80 homolog [KO:K11547]
106628496  CASC5; protein CASC5 isoform X1 [KO:K11542]
102114468  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
102103130  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
102103464  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
102109133  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
102102959  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
102110221  BUB3; mitotic checkpoint protein BUB3 [KO:K02180]
102099698  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
102111529  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
102100434  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
102111298  FZR1; fizzy-related protein homolog [KO:K03364]
102109819  FBXO5; F-box only protein 5 [KO:K10292]
102114594  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102113739  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102103796  CREBBP; CREB-binding protein isoform X2 [KO:K04498] [EC:2.3.1.48]
102103022  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
102108488  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
102109906  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
102099369  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
102099986  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
102101491  TP53; cellular tumor antigen p53 [KO:K04451]
102102492  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102109500  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102109553  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102102468  PCNA; proliferating cell nuclear antigen [KO:K04802]
102104723  SFN; 14-3-3 protein sigma [KO:K06644]
102103508  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
102110514  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
102104005  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
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.
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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
phi03030  DNA replication
phi04010  MAPK signaling pathway
phi04120  Ubiquitin mediated proteolysis
phi04210  Apoptosis
KO pathway
ko04110   
LinkDB

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