KEGG   PATHWAY: sbq04110
Entry
sbq04110                    Pathway                                
Name
Cell cycle - Saimiri boliviensis boliviensis (Bolivian squirrel 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
sbq04110  Cell cycle
sbq04110

Other DBs
GO: 0000278
Organism
Saimiri boliviensis boliviensis (Bolivian squirrel monkey) [GN:sbq]
Gene
101047858  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
101049141  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
101047749  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
101040767  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
101040507  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
101038309  RB1; retinoblastoma-associated protein [KO:K06618]
101050771  RBL1; retinoblastoma-like protein 1 [KO:K04681]
101038159  RBL2; retinoblastoma-like protein 2 isoform X1 [KO:K16332]
101046557  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
101041477  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
101039964  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
101029045  E2F1; transcription factor E2F1 [KO:K17454]
101042612  E2F2; transcription factor E2F2 [KO:K09389]
101034207  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
101052390  E2F4; transcription factor E2F4 isoform X1 [KO:K04682]
101035650  E2F5; transcription factor E2F5 [KO:K04682]
101050972  TFDP1; transcription factor Dp-1 [KO:K04683]
101045140  TFDP2; transcription factor Dp-2 isoform X1 [KO:K09392]
101051107  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
101047980  TGFB1; transforming growth factor beta-1 isoform X2 [KO:K13375]
101044624  TGFB2; transforming growth factor beta-2 isoform X2 [KO:K13376]
101048819  TGFB3; transforming growth factor beta-3 isoform X1 [KO:K13377]
101040653  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
101039593  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
101032066  SMAD4; mothers against decapentaplegic homolog 4 [KO:K04501]
101047066  MYC; myc proto-oncogene protein isoform X2 [KO:K04377]
101048455  ZBTB17; zinc finger and BTB domain-containing protein 17 isoform X4 [KO:K10500]
101038444  cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3 [KO:K06621]
101030939  CDKN2B; cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101041782  CDKN2C; cyclin-dependent kinase 4 inhibitor C [KO:K06622]
101030578  CDKN2D; cyclin-dependent kinase 4 inhibitor D [KO:K06623]
101030975  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
101041919  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
101036684  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
101052282  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
101053477  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
101030146  SKP1; S-phase kinase-associated protein 1 [KO:K03094]
101051291  CUL1; cullin-1 [KO:K03347]
101031903  RBX1; E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
101041621  S-phase kinase-associated protein 2 isoform X2 [KO:K03875]
104652690  CCNA2; cyclin-A2 [KO:K06627]
101040909  CCNA1; cyclin-A1 [KO:K06627]
101031148  CDC6; cell division control protein 6 homolog [KO:K02213]
101032143  CDT1; DNA replication factor Cdt1 [KO:K10727]
101037004  ORC1; origin recognition complex subunit 1 [KO:K02603]
101042142  ORC2; origin recognition complex subunit 2 [KO:K02604]
101027401  ORC3; origin recognition complex subunit 3 isoform X1 [KO:K02605]
101036262  ORC4; origin recognition complex subunit 4 isoform X1 [KO:K02606]
101048898  ORC5; origin recognition complex subunit 5 [KO:K02607]
101050595  ORC6; origin recognition complex subunit 6 [KO:K02608]
101047672  MCM2; DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
101035737  MCM3; DNA replication licensing factor MCM3 isoform X1 [KO:K02541] [EC:5.6.2.3]
101030175  MCM4; DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
101039074  MCM5; DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
101033108  MCM6; DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
101030338  MCM7; DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
101032925  CDC45; cell division control protein 45 homolog isoform X3 [KO:K06628]
101052940  TICRR; treslin [KO:K26117]
101048767  MTBP; mdm2-binding protein [KO:K26116]
101042080  CDC7; cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
101028109  DBF4; protein DBF4 homolog A [KO:K06629]
101049148  DBF4B; protein DBF4 homolog B isoform X1 [KO:K06629]
101035782  CDK1; cyclin-dependent kinase 1 isoform X1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
101049539  G2/mitotic-specific cyclin-B1 [KO:K05868]
101052973  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
101027967  LOW QUALITY PROTEIN: G2/mitotic-specific cyclin-B2-like [KO:K21770]
101044389  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
101050059  CCNB3; G2/mitotic-specific cyclin-B3 [KO:K21771]
101033653  CDC25B; M-phase inducer phosphatase 2 isoform X3 [KO:K05866] [EC:3.1.3.48]
101041558  CDC25C; M-phase inducer phosphatase 3 [KO:K05867] [EC:3.1.3.48]
101047958  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
101035668  14-3-3 protein theta [KO:K16197]
101046355  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
101042265  YWHAQ; 14-3-3 protein theta [KO:K16197]
101040886  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
101036879  YWHAG; 14-3-3 protein gamma [KO:K16198]
101042478  YWHAH; 14-3-3 protein eta [KO:K16198]
101038450  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
101028068  WEE2; wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
101041570  WEE1; wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
101039582  PKMYT1; membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase [KO:K06633] [EC:2.7.11.1]
101032444  CCNH; cyclin-H isoform X2 [KO:K06634]
104650501  LOW QUALITY PROTEIN: cyclin-dependent kinase 7-like [KO:K02202] [EC:2.7.11.22 2.7.11.23]
101028054  ANAPC1; anaphase-promoting complex subunit 1 [KO:K03348]
101053497  ANAPC2; anaphase-promoting complex subunit 2 [KO:K03349]
101030829  CDC27; cell division cycle protein 27 homolog isoform X1 [KO:K03350]
101049272  ANAPC4; anaphase-promoting complex subunit 4 isoform X2 [KO:K03351]
101045597  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
101045358  CDC16; cell division cycle protein 16 homolog [KO:K03353]
101052047  ANAPC7; LOW QUALITY PROTEIN: anaphase-promoting complex subunit 7 [KO:K03354]
101043458  CDC23; cell division cycle protein 23 homolog [KO:K03355]
101038218  ANAPC10; anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
104651978  anaphase-promoting complex subunit 11 [KO:K03358]
101042490  ANAPC13; anaphase-promoting complex subunit 13 [KO:K12456]
101053798  ANAPC15; anaphase-promoting complex subunit 15 [KO:K25228]
101034420  ANAPC16; anaphase-promoting complex subunit 16 [KO:K25229]
101044216  CDC20; cell division cycle protein 20 homolog isoform X1 [KO:K03363]
101036206  LOW QUALITY PROTEIN: securin-like [KO:K06635]
104651299  PTTG2; LOW QUALITY PROTEIN: securin-2 [KO:K06635]
101040159  PTTG1; securin [KO:K06635]
101048054  ESPL1; separin [KO:K02365] [EC:3.4.22.49]
101047907  SMC1B; structural maintenance of chromosomes protein 1B [KO:K06636]
101040339  SMC1A; structural maintenance of chromosomes protein 1A [KO:K06636]
101039531  SMC3; structural maintenance of chromosomes protein 3 [KO:K06669]
101027770  RAD21; double-strand-break repair protein rad21 homolog isoform X1 [KO:K06670]
101040143  STAG2; cohesin subunit SA-2 isoform X1 [KO:K06671]
101046950  STAG1; cohesin subunit SA-1 [KO:K06671]
101049515  ATRX; transcriptional regulator ATRX isoform X1 [KO:K10779]
101028962  LOW QUALITY PROTEIN: uncharacterized protein LOC101028962 [KO:K11273] [EC:5.6.2.7]
101048747  DDX11; probable ATP-dependent RNA helicase DDX11 [KO:K11273] [EC:5.6.2.7]
101039361  NIPBL; nipped-B-like protein isoform X1 [KO:K06672]
101045227  MAU2; MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
101040990  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
101049975  ESCO1; N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
101049003  ESCO2; LOW QUALITY PROTEIN: N-acetyltransferase ESCO2 [KO:K11268] [EC:2.3.1.-]
101029699  PDS5B; sister chromatid cohesion protein PDS5 homolog B [KO:K11267]
101032704  PDS5A; sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
101028942  WAPAL; wings apart-like protein homolog isoform X1 [KO:K25163]
101031294  CDCA5; sororin [KO:K17390]
101051287  AURKB; aurora kinase B isoform X2 [KO:K11479] [EC:2.7.11.1]
101033449  SGOL1; shugoshin-like 1 isoform X1 [KO:K11580]
101028752  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
101037428  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101034311  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101033118  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
101049860  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
101028563  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
101050938  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
101028072  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
101028554  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
101031645  NDC80; kinetochore protein NDC80 homolog [KO:K11547]
101033614  CASC5; protein CASC5 [KO:K11542]
101033953  TTK; dual specificity protein kinase TTK [KO:K08866] [EC:2.7.12.1]
101035986  MAD1L1; mitotic spindle assembly checkpoint protein MAD1 [KO:K06679]
101036641  MAD2L1; mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
101044104  MAD2L2; mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
101052819  BUB1B; mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
101053907  BUB3; mitotic checkpoint protein BUB3 [KO:K02180]
101044372  BUB1; mitotic checkpoint serine/threonine-protein kinase BUB1 isoform X1 [KO:K02178] [EC:2.7.11.1]
101034332  TRIP13; pachytene checkpoint protein 2 homolog [KO:K22399]
101038910  MAD2L1BP; MAD2L1-binding protein [KO:K26093]
101032365  FZR1; fizzy-related protein homolog isoform X2 [KO:K03364]
101034753  FBXO5; LOW QUALITY PROTEIN: F-box only protein 5 [KO:K10292]
101030893  CDC14B; dual specificity protein phosphatase CDC14B isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101045071  CDC14A; dual specificity protein phosphatase CDC14A isoform X2 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101033803  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101050224  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
101053589  PRKDC; DNA-dependent protein kinase catalytic subunit isoform X1 [KO:K06642] [EC:2.7.11.1]
101043200  ATR; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
101040534  ATM; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
101036938  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
101043647  TP53; cellular tumor antigen p53 [KO:K04451]
101030208  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
101039106  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101047513  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
101054404  PCNA; proliferating cell nuclear antigen [KO:K04802]
101038797  SFN; 14-3-3 protein sigma [KO:K06644]
101044792  CHEK1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
101051768  CHEK2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
101041208  CDC25A; M-phase inducer phosphatase 1 [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.
  Journal
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.
  Journal
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
sbq03030  DNA replication
sbq04010  MAPK signaling pathway
sbq04120  Ubiquitin mediated proteolysis
sbq04210  Apoptosis
KO pathway
ko04110   
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