KEGG   PATHWAY: hhv04110
Entry
hhv04110                    Pathway                                
Name
Cell cycle - Hyaena hyaena (striped hyena)
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
hhv04110  Cell cycle
hhv04110

Other DBs
GO: 0000278
Organism
Hyaena hyaena (striped hyena) [GN:hhv]
Gene
120219608  TTK; dual specificity protein kinase TTK isoform X1 [KO:K08866] [EC:2.7.12.1]
120219657  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
120219774  TICRR; treslin [KO:K26117]
120219963  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
120220292  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
120220392  MCM3; DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
120220693  ORC2; origin recognition complex subunit 2 [KO:K02604]
120220748  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
120220759  CDC23; cell division cycle protein 23 homolog [KO:K03355]
120220837  RB1; retinoblastoma-associated protein [KO:K06618]
120220861  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
120221278  SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605]
120221741  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
120221751  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
120221837  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
120222026  SGO1; shugoshin 1 isoform X1 [KO:K11580]
120222162  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
120222270  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
120222367  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
120222773  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
120222958  SMC1A; structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
120223033  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
120223135  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
120223233  CDKN2A; cyclin-dependent kinase inhibitor 2A isoform X1 [KO:K06621]
120223236  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
120223459  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
120223462  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
120224109  CCNH; cyclin-H [KO:K06634]
120224230  DBF4; LOW QUALITY PROTEIN: protein DBF4 homolog A [KO:K06629]
120224489  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
120224881  E2F4; transcription factor E2F4 [KO:K04682]
120225275  CDT1; DNA replication factor Cdt1 [KO:K10727]
120225456  PRKDC; DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
120225462  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
120225537  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
120225924  [KO:K22399]
120226286  ORC5; origin recognition complex subunit 5 [KO:K02607]
120226460  CDC25B; M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
120226610  PCNA; proliferating cell nuclear antigen [KO:K04802]
120226714  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
120227007  CHEK2; serine/threonine-protein kinase Chk2 isoform X1 [KO:K06641] [EC:2.7.11.1]
120227288  [KO:K06671]
120227869  YWHAH; 14-3-3 protein eta [KO:K16198]
120227955  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
120228206  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
120228529  PDS5A; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
120228633  RBL1; retinoblastoma-like protein 1 [KO:K04681]
120228658  [KO:K26116]
120228674  RAD21; double-strand-break repair protein rad21 homolog [KO:K06670]
120228989  CDC6; cell division control protein 6 homolog isoform X1 [KO:K02213]
120229302  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
120229362  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
120229442  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
120229672  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
120229684  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
120229780  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
120229863  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
120229915  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
120230153  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
120230392  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
120230498  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
120230745  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
120230878  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
120231148  YWHAQ; 14-3-3 protein theta [KO:K16197]
120231211  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
120231256  [KO:K26093]
120231386  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
120231446  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
120231474  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
120231585  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
120231597  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
120231725  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
120231992  TGFB3; transforming growth factor beta-3 proprotein isoform X1 [KO:K13377]
120232014  SFN; 14-3-3 protein sigma [KO:K06644]
120232275  KNL1; kinetochore scaffold 1 [KO:K11542]
120232293  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
120232638  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
120232784  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
120232842  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
120232903  E2F2; transcription factor E2F2 [KO:K09389]
120232995  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
120233032  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
120233285  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
120233334  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
120233630  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
120233834  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
120233865  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
120233874  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
120234269  [KO:K06643] [EC:2.3.2.27]
120234320  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
120234500  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:3.6.4.13]
120234569  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
120234672  [KO:K03868] [EC:2.3.2.32]
120234706  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
120235007  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
120235248  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
120235548  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
120235604  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
120235926  ORC1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
120236058  CDC20; cell division cycle protein 20 homolog [KO:K03363]
120236172  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
120236454  [KO:K04498] [EC:2.3.1.48]
120236502  CDC26; anaphase-promoting complex subunit CDC26 isoform X1 [KO:K03359]
120236818  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
120236827  [KO:K03868] [EC:2.3.2.32]
120236900  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
120237069  [KO:K03094]
120237661  ANAPC7; anaphase-promoting complex subunit 7 [KO:K03354]
120237907  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
120237943  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
120238030  CCNA2; cyclin-A2 [KO:K06627]
120238083  ORC6; origin recognition complex subunit 6 [KO:K02608]
120238408  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
120238508  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
120238518  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
120238692  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
120238800  CDC45; cell division control protein 45 homolog [KO:K06628]
120239075  NDC80; kinetochore protein NDC80 homolog isoform X1 [KO:K11547]
120239308  YWHAG; 14-3-3 protein gamma [KO:K16198]
120239528  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
120240003  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
120240035  WEE1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
120240152  CDCA5; sororin isoform X1 [KO:K17390]
120240155  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
120240558  [KO:K06671]
120240587  PTTG1; securin isoform X1 [KO:K06635]
120240620  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
120240795  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
120240828  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
120240874  MYC; myc proto-oncogene protein [KO:K04377]
120241525  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
120242073  FZR1; fizzy-related protein homolog isoform X1 [KO:K03364]
120242325  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
120242603  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
120242654  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
120242733  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
120242807  E2F1; transcription factor E2F1 [KO:K17454]
120242922  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
120243258  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
120243735  HDAC2; LOW QUALITY PROTEIN: histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
120243919  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
120244139  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
120244153  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
120244162  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
120244248  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
120244301  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
120244409  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
120244579  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
120245010  CCNA1; cyclin-A1 [KO:K06627]
120245117  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
120245536  YWHAE; 14-3-3 protein epsilon [KO:K06630]
120246140  E2F5; transcription factor E2F5 isoform X1 [KO:K04682]
120246345  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
120246394  CUL1; cullin-1 [KO:K03347]
120247214  [KO:K12456]
120247237  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
120247482  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
120247570  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
120247732  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
120247819  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
120247948  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
120247955  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
120248012  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
120248226  STAG1; cohesin subunit SA-1 [KO:K06671]
120249038  [KO:K03094]
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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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.
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Oncogene 25:5263-7 (2006)
DOI:10.1038/sj.onc.1209680
Reference
PMID:15838516
  Authors
Cobrinik D
  Title
Pocket proteins and cell cycle control.
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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?
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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
  Authors
Klein EA, Assoian RK
  Title
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)
DOI:10.1016/S0092-8674(03)00432-X
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)
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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
  Authors
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
PMID:9889196
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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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  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
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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
  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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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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  Title
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
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  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
hhv03030  DNA replication
hhv04010  MAPK signaling pathway
hhv04120  Ubiquitin mediated proteolysis
hhv04210  Apoptosis
KO pathway
ko04110   

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