KEGG   PATHWAY: mmur04110
Entry
mmur04110                   Pathway                                
Name
Cell cycle - Microcebus murinus (gray mouse lemur)
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
mmur04110  Cell cycle
mmur04110

Other DBs
GO: 0000278
Organism
Microcebus murinus (gray mouse lemur) [GN:mmur]
Gene
105867511  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
105881459  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
105875858  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
105877995  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
105879410  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
105855966  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
105865895  RBL1; retinoblastoma-like protein 1 isoform X1 [KO:K04681]
105875529  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
105865709  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
105871810  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
105864982  HDAC2; LOW QUALITY PROTEIN: histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
105866012  E2F1; transcription factor E2F1 [KO:K17454]
105863547  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
105865199  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105876538  E2F5; LOW QUALITY PROTEIN: transcription factor E2F5 [KO:K04682]
105859043  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
105871903  TFDP1; transcription factor Dp-1 isoform X1 [KO:K04683]
105870052  TFDP2; transcription factor Dp-2 isoform X6 [KO:K09392]
105879917  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105869115  TGFB1; transforming growth factor beta-1 isoform X1 [KO:K13375]
105868760  TGFB2; transforming growth factor beta-2 isoform X1 [KO:K13376]
105858956  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
105860538  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
105857966  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
105874233  SMAD4; mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
105882748  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
105870453  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X1 [KO:K10500]
105874194  cyclin-dependent kinase inhibitor 2A [KO:K06621]
105874193  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
105877534  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
105885583  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
105876702  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
105867526  CDKN1C; cyclin-dependent kinase inhibitor 1C [KO:K09993]
105861439  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105875662  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
105877006  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
105864946  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
105869977  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
105873323  CUL1; cullin-1 [KO:K03347]
105858549  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
105855459  SKP2; S-phase kinase-associated protein 2 isoform X1 [KO:K03875]
105882110  CCNA2; cyclin-A2 [KO:K06627]
105862090  CCNA1; cyclin-A1 [KO:K06627]
105872082  CDC6; cell division control protein 6 homolog [KO:K02213]
105855892  CDT1; DNA replication factor Cdt1 [KO:K10727]
105877559  ORC1; origin recognition complex subunit 1 isoform X1 [KO:K02603]
105856971  ORC2; origin recognition complex subunit 2 isoform X1 [KO:K02604]
105863597  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
105860223  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
105861504  ORC5; origin recognition complex subunit 5 [KO:K02607]
105876219  ORC6; origin recognition complex subunit 6 isoform X1 [KO:K02608]
105868771  DNA replication licensing factor MCM2-like [KO:K02540] [EC:5.6.2.3]
105857919  DNA replication licensing factor MCM2-like [KO:K02540] [EC:5.6.2.3]
105869198  MCM3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
105885242  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
105883691  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
105857625  MCM6; DNA replication licensing factor MCM6 isoform X1 [KO:K02542] [EC:5.6.2.3]
105868306  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
105877738  CDC45; cell division control protein 45 homolog isoform X1 [KO:K06628]
105870618  TICRR; treslin [KO:K26117]
105865331  MTBP; mdm2-binding protein [KO:K26116]
105885713  CDC7; cell division cycle 7-related protein kinase [KO:K02214] [EC:2.7.11.1]
105879368  DBF4; protein DBF4 homolog A isoform X1 [KO:K06629]
105883568  DBF4B; protein DBF4 homolog B [KO:K06629]
105870266  CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
105881287  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
105881385  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
105867163  CCNB3; G2/mitotic-specific cyclin-B3 isoform X1 [KO:K21771]
105866002  CDC25B; M-phase inducer phosphatase 2 [KO:K05866] [EC:3.1.3.48]
105862589  CDC25C; M-phase inducer phosphatase 3 isoform X1 [KO:K05867] [EC:3.1.3.48]
105882933  YWHAQ; 14-3-3 protein theta [KO:K16197]
105869900  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
105879966  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
105857911  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
105868392  YWHAG; 14-3-3 protein gamma [KO:K16198]
105870971  YWHAH; 14-3-3 protein eta [KO:K16198]
105879722  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
105881977  WEE1; wee1-like protein kinase [KO:K06632] [EC:2.7.11.1]
105873255  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
105859742  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
105880428  CCNH; cyclin-H isoform X1 [KO:K06634]
105881326  CDK7; cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
105859176  ANAPC1; anaphase-promoting complex subunit 1 isoform X1 [KO:K03348]
105882248  anaphase-promoting complex subunit 2 isoform X1 [KO:K03349]
105863670  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
105856046  ANAPC4; anaphase-promoting complex subunit 4 isoform X1 [KO:K03351]
105880913  ANAPC5; anaphase-promoting complex subunit 5 isoform X3 [KO:K03352]
105871895  CDC16; cell division cycle protein 16 homolog isoform X1 [KO:K03353]
105880640  LOW QUALITY PROTEIN: anaphase-promoting complex subunit 7-like [KO:K03354]
105880834  ANAPC7; anaphase-promoting complex subunit 7 [KO:K03354]
105862495  CDC23; LOW QUALITY PROTEIN: cell division cycle protein 23 homolog [KO:K03355]
105881854  ANAPC10; anaphase-promoting complex subunit 10 [KO:K03357]
105884950  ANAPC11; anaphase-promoting complex subunit 11 [KO:K03358]
105873707  CDC26; anaphase-promoting complex subunit CDC26 isoform X1 [KO:K03359]
105884074  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
105860330  ANAPC15; anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
105870172  ANAPC16; anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
105877421  CDC20; cell division cycle protein 20 homolog [KO:K03363]
105883285  PTTG1; securin isoform X1 [KO:K06635]
105870726  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
105867399  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
105861238  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
105874933  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
105863707  RAD21; double-strand-break repair protein rad21 homolog isoform X1 [KO:K06670]
105860712  STAG2; LOW QUALITY PROTEIN: cohesin subunit SA-2 [KO:K06671]
105884058  STAG1; cohesin subunit SA-1 isoform X1 [KO:K06671]
105866147  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
105879286  DDX11; ATP-dependent DNA helicase DDX11 isoform X1 [KO:K11273] [EC:5.6.2.7]
105855462  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
105858355  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
105882189  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
105860905  ESCO1; N-acetyltransferase ESCO1 isoform X1 [KO:K11268] [EC:2.3.1.-]
105877132  ESCO2; N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
105864324  PDS5B; sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
105865407  PDS5A; sister chromatid cohesion protein PDS5 homolog A isoform X2 [KO:K11267]
105884268  WAPL; wings apart-like protein homolog isoform X1 [KO:K25163]
105878504  CDCA5; sororin isoform X1 [KO:K17390]
105877184  AURKB; aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
105881570  SGO1; shugoshin 1 isoform X1 [KO:K11580]
105882048  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
105869976  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
105882885  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
105862927  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
105861072  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
105875833  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
105878328  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
105878495  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
105880541  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
105861018  NDC80; kinetochore protein NDC80 homolog isoform X1 [KO:K11547]
105872448  KNL1; protein CASC5 isoform X1 [KO:K11542]
105873859  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
105868296  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 isoform X1 [KO:K06679]
105860831  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
105882722  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
105872430  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta isoform X1 [KO:K06637] [EC:2.7.11.1]
105880346  BUB3; mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
105859200  BUB1; LOW QUALITY PROTEIN: mitotic checkpoint serine/threonine-protein kinase BUB1 [KO:K02178] [EC:2.7.11.1]
105876461  TRIP13; pachytene checkpoint protein 2 homolog isoform X1 [KO:K22399]
105875809  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
105873998  FZR1; fizzy-related protein homolog [KO:K03364]
105862106  FBXO5; F-box only protein 5 isoform X1 [KO:K10292]
105883795  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
105862375  CDC14A; dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
105859673  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
105858560  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
105885240  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
105870060  ATR; serine/threonine-protein kinase ATR isoform X1 [KO:K06640] [EC:2.7.11.1]
105876116  ATM; LOW QUALITY PROTEIN: serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
105884627  LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
105877486  TP53; cellular tumor antigen p53 [KO:K04451]
105873984  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
105876174  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
105872856  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
105866046  PCNA; proliferating cell nuclear antigen [KO:K04802]
105863511  SFN; 14-3-3 protein sigma [KO:K06644]
105881584  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
105870892  CHEK2; LOW QUALITY PROTEIN: serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
105874913  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.
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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)
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
mmur03030  DNA replication
mmur04010  MAPK signaling pathway
mmur04120  Ubiquitin mediated proteolysis
mmur04210  Apoptosis
KO pathway
ko04110   
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