KEGG   PATHWAY: rro04110
Entry
rro04110                    Pathway                                
Name
Cell cycle - Rhinopithecus roxellana (golden snub-nosed monkey)
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
rro04110  Cell cycle
rro04110

Other DBs
GO: 0000278
Organism
Rhinopithecus roxellana (golden snub-nosed monkey) [GN:rro]
Gene
104653937  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
104654116  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
104654271  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
104654275  CDKN2A; cyclin-dependent kinase inhibitor 2A isoform X1 [KO:K06621]
104654352  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
104654440  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
104654592  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
104654724  DBF4B; protein DBF4 homolog B [KO:K06629]
104654770  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
104654803  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
104654968  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
104655109  CDC6; cell division control protein 6 homolog isoform X3 [KO:K02213]
104655197  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
104655277  CCNH; cyclin-H isoform X1 [KO:K06634]
104655429  ORC6; origin recognition complex subunit 6 [KO:K02608]
104655461  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
104655488  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
104655647  E2F4; transcription factor E2F4 [KO:K04682]
104655806  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
104656048  CDT1; DNA replication factor Cdt1 [KO:K10727]
104656129  E2F2; LOW QUALITY PROTEIN: transcription factor E2F2 [KO:K09389]
104656155  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
104656307  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
104656678  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
104656947  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
104657112  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
104657306  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
104657617  BUB3; mitotic checkpoint protein BUB3 isoform X2 [KO:K02180]
104657633  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
104657634  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
104657832  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
104658187  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
104658229  FBXO5; F-box only protein 5 isoform X2 [KO:K10292]
104658250  RBL2; retinoblastoma-like protein 2 [KO:K16332]
104658253  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
104658667  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
104658979  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
104658998  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
104659224  [KO:K11580]
104659656  [KO:K11542]
104659672  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
104659708  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
104659809  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
104659810  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
104660298  E2F1; transcription factor E2F1 [KO:K17454]
104660331  CCNE2; G1/S-specific cyclin-E2 isoform X2 [KO:K06626]
104660365  YWHAH; 14-3-3 protein eta [KO:K16198]
104660482  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
104660552  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
104660768  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
104661662  TP53; cellular tumor antigen p53 [KO:K04451]
104661685  AURKB; aurora kinase B isoform X2 [KO:K11479] [EC:2.7.11.1]
104661791  CCNA2; cyclin-A2 [KO:K06627]
104662024  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
104662078  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
104662252  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
104662521  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
104662580  SMAD3; mothers against decapentaplegic homolog 3 isoform X2 [KO:K23605]
104662760  RB1; retinoblastoma-associated protein [KO:K06618]
104662833  CDCA5; sororin [KO:K17390]
104662840  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
104663058  MCM3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
104663372  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
104663564  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
104663569  ANAPC13; anaphase-promoting complex subunit 13 isoform X2 [KO:K12456]
104663595  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
104663679  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
104664346  PTTG2; LOW QUALITY PROTEIN: securin-2 [KO:K06635]
104664955  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X2 [KO:K06679]
104665156  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
104665288  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
104665426  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
104665446  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
104665624  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
104665705  SGO1; shugoshin 1 isoform X2 [KO:K11580]
104665985  [KO:K17390]
104666274  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
104667014  CUL1; cullin-1 [KO:K03347]
104667309  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
104667330  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
104667359  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
104667496  PTTG1; securin [KO:K06635]
104667769  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
104667810  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
104667867  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
104668037  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
104668148  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X2 [KO:K10500]
104668221  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
104668343  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
104668704  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
104669028  CDC20; cell division cycle protein 20 homolog [KO:K03363]
104669164  ORC1; origin recognition complex subunit 1 [KO:K02603]
104669493  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
104669632  ANAPC2; anaphase-promoting complex subunit 2 isoform X1 [KO:K03349]
104669939  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
104670208  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
104670310  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
104670446  ORC2; origin recognition complex subunit 2 [KO:K02604]
104670470  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
104670601  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
104670827  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
104670890  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
104671299  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
104671361  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
104671369  [KO:K04683]
104671382  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
104671474  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
104672289  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
104672324  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
104672448  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
104672685  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
104672737  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
104672831  DDX11; ATP-dependent DNA helicase DDX11 isoform X7 [KO:K11273] [EC:3.6.4.13]
104672916  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
104673256  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
104673260  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
104673455  RBX1; E3 ubiquitin-protein ligase RBX1 isoform X1 [KO:K03868] [EC:2.3.2.32]
104673596  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
104673700  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
104673923  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
104673941  [KO:K11268] [EC:2.3.1.-]
104674064  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
104674348  TICRR; treslin [KO:K26117]
104674579  PCNA; proliferating cell nuclear antigen [KO:K04802]
104674594  CDC25B; M-phase inducer phosphatase 2 isoform X2 [KO:K05866] [EC:3.1.3.48]
104674798  MYC; myc proto-oncogene protein [KO:K04377]
104674806  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
104675079  [KO:K17390]
104675211  YWHAQ; 14-3-3 protein theta [KO:K16197]
104675626  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
104675629  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
104675742  SFN; 14-3-3 protein sigma [KO:K06644]
104675825  ORC5; origin recognition complex subunit 5 [KO:K02607]
104676086  TGFB1; transforming growth factor beta-1 proprotein isoform X2 [KO:K13375]
104676600  MTBP; mdm2-binding protein [KO:K26116]
104676866  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
104677152  CDKN1C; cyclin-dependent kinase inhibitor 1C isoform X1 [KO:K09993]
104677168  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
104677263  [KO:K03094]
104677337  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
104677352  [KO:K06067] [EC:3.5.1.98]
104677599  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
104677942  CCNA1; cyclin-A1 isoform X1 [KO:K06627]
104678862  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
104679074  PDS5A; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
104679301  WEE1; LOW QUALITY PROTEIN: wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
104679571  [KO:K03350]
104680409  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
104680654  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
104680782  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
104680848  CDC14C; dual specificity protein phosphatase CDC14C [KO:K06639] [EC:3.1.3.16 3.1.3.48]
104680990  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
104681212  YWHAG; 14-3-3 protein gamma [KO:K16198]
104681613  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
104681723  CDC23; cell division cycle protein 23 homolog [KO:K03355]
104681726  CDC25C; M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
104682058  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
104682118  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
104682194  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
104682344  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
104682469  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
104682750  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
104682880  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
115892000  [KO:K04683]
115893879  [KO:K16197]
115893891  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
115894564  [KO:K04683]
115895835  [KO:K04683]
115896370  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
115899663  [KO:K11268] [EC:2.3.1.-]
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.
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EMBO J 16:343-54 (1997)
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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
rro03030  DNA replication
rro04010  MAPK signaling pathway
rro04120  Ubiquitin mediated proteolysis
rro04210  Apoptosis
KO pathway
ko04110   

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