KEGG   PATHWAY: pale04110
Entry
pale04110                   Pathway                                
Name
Cell cycle - Pteropus alecto (black flying fox)
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
pale04110  Cell cycle
pale04110

Other DBs
GO: 0000278
Organism
Pteropus alecto (black flying fox) [GN:pale]
Gene
102877831  ZBTB17; zinc finger and BTB domain-containing protein 17 [KO:K10500]
102877842  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
102878098  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
102878191  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102878200  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
102878300  ORC6; origin recognition complex subunit 6 [KO:K02608]
102878533  DBF4; protein DBF4 homolog A isoform X2 [KO:K06629]
102878536  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
102878861  YWHAH; 14-3-3 protein eta [KO:K16198]
102878932  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
102879054  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
102879595  MTBP; mdm2-binding protein isoform X1 [KO:K26116]
102880062  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
102880081  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
102880085  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
102880158  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
102880240  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
102880559  CDC6; cell division control protein 6 homolog isoform X1 [KO:K02213]
102880585  CDC20; cell division cycle protein 20 homolog [KO:K03363]
102880611  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102880620  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
102880695  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
102880932  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
102880967  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X1 [KO:K11267]
102881017  CDC27; cell division cycle protein 27 homolog isoform X5 [KO:K03350]
102881042  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
102881266  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
102881295  TGFB2; transforming growth factor beta-2 isoform X2 [KO:K13376]
102881793  TFDP1; transcription factor Dp-1 isoform X2 [KO:K04683]
102881804  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
102881866  TICRR; treslin [KO:K26117]
102881884  CCND3; G1/S-specific cyclin-D3 [KO:K10152]
102881997  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
102882260  CCNE1; LOW QUALITY PROTEIN: G1/S-specific cyclin-E1 [KO:K06626]
102882358  CHEK2; LOW QUALITY PROTEIN: serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
102882405  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
102882411  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
102882441  GSK3B; glycogen synthase kinase-3 beta isoform X4 [KO:K03083] [EC:2.7.11.26]
102882545  RBL2; retinoblastoma-like protein 2 [KO:K16332]
102882576  ORC1; origin recognition complex subunit 1 [KO:K02603]
102882657  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
102882717  BUB3; mitotic checkpoint protein BUB3 [KO:K02180]
102882823  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
102882912  CDC26; anaphase-promoting complex subunit CDC26 [KO:K03359]
102882975  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B isoform X1 [KO:K13728]
102882999  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
102883003  NDC80; kinetochore protein NDC80 homolog isoform X2 [KO:K11547]
102883058  CCNH; cyclin-H isoform X2 [KO:K06634]
102883422  SMC3; structural maintenance of chromosomes protein 3 isoform X1 [KO:K06669]
102883454  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
102884154  TGFB1; transforming growth factor beta-1 [KO:K13375]
102884281  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
102884397  ANAPC5; anaphase-promoting complex subunit 5 isoform X2 [KO:K03352]
102884398  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
102884459  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
102885289  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102885303  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
102885330  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102885538  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
102885716  PTTG1; securin isoform X1 [KO:K06635]
102885734  ANAPC7; anaphase-promoting complex subunit 7 isoform X1 [KO:K03354]
102885763  STAG2; cohesin subunit SA-2 isoform X3 [KO:K06671]
102885790  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
102885814  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
102885835  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
102885939  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
102886172  CREBBP; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
102886357  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
102886440  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
102886521  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
102886725  CDT1; DNA replication factor Cdt1 isoform X2 [KO:K10727]
102887013  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
102887109  CUL1; cullin-1 [KO:K03347]
102887239  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102887618  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
102887771  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
102888011  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
102888607  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
102888699  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
102889054  ORC3; origin recognition complex subunit 3 [KO:K02605]
102889083  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
102889293  ORC5; origin recognition complex subunit 5 isoform X7 [KO:K02607]
102889312  ATRX; transcriptional regulator ATRX isoform X5 [KO:K10779]
102889339  ATR; LOW QUALITY PROTEIN: serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
102889604  TP53; cellular tumor antigen p53 [KO:K04451]
102889704  SFN; 14-3-3 protein sigma [KO:K06644]
102890018  PCNA; proliferating cell nuclear antigen [KO:K04802]
102890060  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
102890110  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
102890192  FZR1; fizzy-related protein homolog [KO:K03364]
102890278  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
102890564  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
102890664  CCNA1; cyclin-A1 [KO:K06627]
102890938  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
102890991  ANAPC15; anaphase-promoting complex subunit 15 isoform X2 [KO:K25228]
102891038  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
102891390  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
102891438  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
102891468  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
102891550  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
102891797  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
102891858  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
102891938  CCNB3; G2/mitotic-specific cyclin-B3 isoform X2 [KO:K21771]
102891987  ESCO2; N-acetyltransferase ESCO2 isoform X1 [KO:K11268] [EC:2.3.1.-]
102892024  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X4 [KO:K11267]
102892440  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
102892497  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
102892539  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
102892640  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
102893019  RB1; retinoblastoma-associated protein [KO:K06618]
102893112  CDC25B; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
102893142  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
102893263  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
102893304  TGFB3; transforming growth factor beta-3 [KO:K13377]
102893397  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
102893437  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
102893655  CDCA5; sororin isoform X2 [KO:K17390]
102893928  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
102893955  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
102894049  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102894080  CCNA2; cyclin-A2 [KO:K06627]
102894193  CDC25C; M-phase inducer phosphatase 3 isoform X3 [KO:K05867] [EC:3.1.3.48]
102894222  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102894232  [KO:K02537]
102894269  KNL1; kinetochore scaffold 1 [KO:K11542]
102894398  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X2 [KO:K06633] [EC:2.7.11.1]
102894487  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
102894826  YWHAQ; 14-3-3 protein theta [KO:K16197]
102894891  E2F4; transcription factor E2F4 isoform X2 [KO:K04682]
102894926  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
102894958  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
102895200  E2F5; transcription factor E2F5 [KO:K04682]
102895268  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
102895276  E2F1; transcription factor E2F1 [KO:K17454]
102895279  CDC23; cell division cycle protein 23 homolog [KO:K03355]
102895334  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
102895399  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
102895401  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
102895426  YWHAG; 14-3-3 protein gamma [KO:K16198]
102895524  MYC; myc proto-oncogene protein [KO:K04377]
102895542  ESPL1; separin isoform X1 [KO:K02365] [EC:3.4.22.49]
102895801  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
102895947  ABL1; tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
102896053  AURKB; LOW QUALITY PROTEIN: aurora kinase B [KO:K11479] [EC:2.7.11.1]
102896082  TFDP2; transcription factor Dp-2 isoform X4 [KO:K09392]
102896272  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102896422  [KO:K06621]
102896980  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
102897091  SGO1; shugoshin 1 isoform X1 [KO:K11580]
102897127  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
102897196  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
102897562  DDX11; ATP-dependent DNA helicase DDX11 isoform X2 [KO:K11273] [EC:3.6.4.13]
102897650  TTK; dual specificity protein kinase TTK isoform X3 [KO:K08866] [EC:2.7.12.1]
102897902  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
102898407  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
102898588  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
102898938  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
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
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Welch PJ, Wang JY
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A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
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Cell 75:779-90 (1993)
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Reference
PMID:16936746
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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
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Cobrinik D
  Title
Pocket proteins and cell cycle control.
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Oncogene 24:2796-809 (2005)
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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)
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Reference
PMID:19020303
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Klein EA, Assoian RK
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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
  Authors
Sherr CJ, Roberts JM
  Title
CDK inhibitors: positive and negative regulators of G1-phase progression.
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Genes Dev 13:1501-12 (1999)
DOI:10.1101/gad.13.12.1501
Reference
PMID:12809600
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Shi Y, Massague J.
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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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Reference
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
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.
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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)
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Reference
PMID:11099028
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Vogelstein B, Lane D, Levine AJ
  Title
Surfing the p53 network.
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Nature 408:307-10 (2000)
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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
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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
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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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Reference
PMID:15876871
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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
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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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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
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Regulation of the human p21/WAF1/Cip1 promoter in hepatic cells by functional interactions between Sp1 and Smad family members.
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Proc Natl Acad Sci U S A 95:6733-8 (1998)
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Reference
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  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
pale03030  DNA replication
pale04010  MAPK signaling pathway
pale04120  Ubiquitin mediated proteolysis
pale04210  Apoptosis
KO pathway
ko04110   

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