KEGG   PATHWAY: phas04110
Entry
phas04110                   Pathway                                
Name
Cell cycle - Phyllostomus hastatus (greater spear-nosed bat)
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
phas04110  Cell cycle
phas04110

Other DBs
GO: 0000278
Organism
Phyllostomus hastatus (greater spear-nosed bat) [GN:phas]
Gene
123804636  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
123804941  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
123805403  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
123805724  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
123805822  E2F4; transcription factor E2F4 [KO:K04682]
123805823  [KO:K04682]
123805874  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
123806047  ORC6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
123806192  CDT1; DNA replication factor Cdt1 [KO:K10727]
123806362  YWHAG; 14-3-3 protein gamma [KO:K16198]
123806501  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
123806607  CDC45; cell division control protein 45 homolog [KO:K06628]
123807079  [KO:K04498] [EC:2.3.1.48]
123807138  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
123807327  CDKN1C; cyclin-dependent kinase inhibitor 1C isoform X1 [KO:K09993]
123807483  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
123807485  TFDP1; transcription factor Dp-1 [KO:K04683]
123807652  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
123808039  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
123808094  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
123808140  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
123808254  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
123808416  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
123808515  [KO:K16197]
123808708  KNL1; kinetochore scaffold 1 [KO:K11542]
123808879  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
123809286  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
123809412  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
123809443  TP53; cellular tumor antigen p53 [KO:K04451]
123809803  TICRR; treslin isoform X1 [KO:K26117]
123809892  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
123809960  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
123810035  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
123810371  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
123810645  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
123810685  PTTG1; securin isoform X1 [KO:K06635]
123810780  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
123811001  YWHAH; 14-3-3 protein eta [KO:K16198]
123811089  CDC23; cell division cycle protein 23 homolog isoform X1 [KO:K03355]
123811100  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
123811515  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
123811601  ORC5; origin recognition complex subunit 5 [KO:K02607]
123811650  BUB1; LOW QUALITY PROTEIN: mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
123811874  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
123812449  [KO:K11273] [EC:5.6.2.7]
123812897  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
123812935  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
123813020  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
123813040  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
123813111  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
123813217  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
123813418  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
123813456  DDX11; LOW QUALITY PROTEIN: ATP-dependent DNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
123813832  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
123813867  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
123813874  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
123813913  [KO:K12456]
123813988  CCNA2; cyclin-A2 [KO:K06627]
123814100  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
123814160  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
123814196  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
123814383  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
123814705  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
123814839  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
123815031  E2F1; transcription factor E2F1 [KO:K17454]
123815084  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
123815209  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
123815383  PCNA; proliferating cell nuclear antigen [KO:K04802]
123815560  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
123815585  CUL1; cullin-1 [KO:K03347]
123815688  PDS5A; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
123815883  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
123816025  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
123816172  SMC1B; structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
123816194  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
123816474  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
123816661  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
123816919  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
123817197  DBF4B; protein DBF4 homolog B [KO:K06629]
123817244  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
123817391  CDC6; cell division control protein 6 homolog isoform X1 [KO:K02213]
123818096  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
123818226  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
123818512  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
123818741  RB1; retinoblastoma-associated protein [KO:K06618]
123818780  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
123818843  CCNA1; cyclin-A1 [KO:K06627]
123819102  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
123819439  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
123819579  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
123819979  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
123820004  [KO:K06621]
123820888  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
123820904  ANAPC16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
123820943  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
123821479  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
123821502  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
123821560  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
123821699  [KO:K26093]
123821731  TTK; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
123821989  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
123821996  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
123822040  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
123822094  ANAPC7; anaphase-promoting complex subunit 7 [KO:K03354]
123822234  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
123822462  YWHAQ; 14-3-3 protein theta [KO:K16197]
123823167  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
123823364  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
123823439  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
123823713  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
123824006  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
123824076  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
123824185  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
123824359  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
123824485  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
123824539  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
123824694  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
123824735  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
123824871  CCNH; cyclin-H isoform X1 [KO:K06634]
123824935  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
123824973  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
123825417  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
123825749  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
123825760  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
123825859  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
123825966  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
123826060  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
123826113  ESCO1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
123826176  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
123826250  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
123827058  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
123827255  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
123827720  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
123828168  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
123828339  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
123828891  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
123828935  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
123829302  CDCA5; sororin isoform X1 [KO:K17390]
123829552  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
123829562  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
123829811  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
123830464  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
123830474  ORC1; origin recognition complex subunit 1 [KO:K02603]
123830479  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
123830645  SGO1; shugoshin 1 isoform X1 [KO:K11580]
123830717  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
123830798  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
123831747  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
123831782  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
123831848  SFN; 14-3-3 protein sigma [KO:K06644]
123831879  CDC20; cell division cycle protein 20 homolog [KO:K03363]
123832315  E2F2; transcription factor E2F2 [KO:K09389]
123832338  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
123832554  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
123832789  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
123833042  [KO:K04802]
123833064  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
123833091  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
123833290  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
123833339  MYC; myc proto-oncogene protein [KO:K04377]
123833374  [KO:K26116]
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
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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.
  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.
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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.
  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.
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Proc Natl Acad Sci U S A 100:10231-6 (2003)
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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
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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)
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Reference
PMID:9889196
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  Title
Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization.
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EMBO J 18:396-410 (1999)
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Reference
PMID:17018296
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Sheu YJ, Stillman B
  Title
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)
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
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  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)
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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)
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Reference
PMID:12573239
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Uhlmann F
  Title
Chromosome cohesion and separation: from men and molecules.
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Curr Biol 13:R104-14 (2003)
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Reference
PMID:15568976
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Stegmeier F, Amon A
  Title
Closing mitosis: the functions of the Cdc14 phosphatase and its regulation.
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Annu Rev Genet 38:203-32 (2004)
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Reference
PMID:9618481
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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)
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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
phas03030  DNA replication
phas04010  MAPK signaling pathway
phas04120  Ubiquitin mediated proteolysis
phas04210  Apoptosis
KO pathway
ko04110   

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