KEGG   PATHWAY: aam04110
Entry
aam04110                    Pathway                                
Name
Cell cycle - Apteryx mantelli mantelli (North Island brown kiwi)
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
aam04110  Cell cycle
aam04110

Other DBs
GO: 0000278
Organism
Apteryx mantelli mantelli (North Island brown kiwi) [GN:aam]
Gene
106482119  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
106482329  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
106482441  MAD2L2; MAD2 mitotic arrest deficient-like 2 (yeast) [KO:K13728]
106482774  MCM2; minichromosome maintenance complex component 2 [KO:K02540] [EC:5.6.2.3]
106482877  TGFB3; transforming growth factor beta 3 [KO:K13377]
106482966  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
106483014  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
106483200  RBL2; RB transcriptional corepressor like 2 [KO:K16332]
106483218  ORC6; origin recognition complex subunit 6 [KO:K02608]
106483300  CCNE1; cyclin E1 [KO:K06626]
106483392  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
106483575  SGO1; shugoshin 1 [KO:K11580]
106483609  DBF4; DBF4 zinc finger [KO:K06629]
106483627  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
106483881  CCNE2; cyclin E2 [KO:K06626]
106483898  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
106483918  [KO:K25228]
106483949  CCND3; cyclin D3 [KO:K10152]
106483968  [KO:K04402]
106484396  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
106484407  [KO:K05868]
106484508  E2F4; E2F transcription factor 4 [KO:K04682]
106484658  NDC80; NDC80, kinetochore complex component [KO:K11547]
106484760  ESCO1; establishment of sister chromatid cohesion N-acetyltransferase 1 [KO:K11268] [EC:2.3.1.-]
106484790  MCM7; minichromosome maintenance complex component 7 [KO:K02210] [EC:5.6.2.3]
106485432  MAD2L1BP; MAD2L1 binding protein [KO:K26093]
106485433  [KO:K26093]
106485590  SFN; stratifin [KO:K06644]
106485692  STAG1; stromal antigen 1 [KO:K06671]
106485832  ATR; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
106485867  ORC5; origin recognition complex subunit 5 [KO:K02607]
106485889  TFDP2; transcription factor Dp-2 [KO:K09392]
106486014  FZR1; fizzy/cell division cycle 20 related 1 [KO:K03364]
106486072  ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
106486140  E2F2; E2F transcription factor 2 [KO:K09389]
106486200  PLK1; polo like kinase 1 [KO:K06631] [EC:2.7.11.21]
106486310  YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
106486420  CDC6; cell division cycle 6 [KO:K02213]
106486494  ESCO2; establishment of sister chromatid cohesion N-acetyltransferase 2 [KO:K11268] [EC:2.3.1.-]
106486565  CDK7; cyclin dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
106486730  BUB1B; BUB1 mitotic checkpoint serine/threonine kinase B [KO:K06637] [EC:2.7.11.1]
106486746  KNL1; kinetochore scaffold 1 [KO:K11542]
106486837  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
106486844  CDC45; cell division cycle 45 [KO:K06628]
106486975  CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
106487187  SKP1; S-phase kinase associated protein 1 [KO:K03094]
106487221  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
106487224  CDC25C; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
106487237  CDC23; cell division cycle 23 [KO:K03355]
106487512  [KO:K05866] [EC:3.1.3.48]
106487565  STAG2; stromal antigen 2 [KO:K06671]
106487670  SMAD3; SMAD family member 3 [KO:K23605]
106487710  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
106488008  ESPL1; extra spindle pole bodies like 1, separase [KO:K02365] [EC:3.4.22.49]
106488223  [KO:K04498] [EC:2.3.1.48]
106488273  WEE2; WEE1 homolog 2 [KO:K06632] [EC:2.7.11.1]
106488571  SMC1B; structural maintenance of chromosomes 1B [KO:K06636]
106488643  DDX11; DEAD/H-box helicase 11 [KO:K11273] [EC:3.6.4.13]
106488755  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
106488827  MCM5; minichromosome maintenance complex component 5 [KO:K02209] [EC:5.6.2.3]
106488961  CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624]
106488968  RBX1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
106488969  [KO:K06625]
106489167  RB1; RB transcriptional corepressor 1 [KO:K06618]
106489314  ATRX; ATRX, chromatin remodeler [KO:K10779]
106489562  CCND2; cyclin D2 [KO:K10151]
106489666  ORC3; origin recognition complex subunit 3 [KO:K02605]
106489693  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
106489724  TTK; TTK protein kinase [KO:K08866] [EC:2.7.12.1]
106490140  PDS5A; PDS5 cohesin associated factor A [KO:K11267]
106490440  TGFB2; transforming growth factor beta 2 [KO:K13376]
106490443  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
106491022  TRIP13; thyroid hormone receptor interactor 13 [KO:K22399]
106491085  ORC1; origin recognition complex subunit 1 [KO:K02603]
106491237  [KO:K06671]
106491387  ZBTB17; zinc finger and BTB domain containing 17 [KO:K10500]
106491420  CDT1; chromatin licensing and DNA replication factor 1 [KO:K10727]
106491607  CDKN2C; cyclin dependent kinase inhibitor 2C [KO:K06622]
106491842  MAD2L1; MAD2 mitotic arrest deficient-like 1 (yeast) [KO:K02537]
106492064  CCNA2; cyclin A2 [KO:K06627]
106492140  ANAPC10; anaphase promoting complex subunit 10 [KO:K03357]
106492459  ORC2; origin recognition complex subunit 2 [KO:K02604]
106492658  ANAPC16; anaphase promoting complex subunit 16 [KO:K25229]
106492744  CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
106492770  [KO:K02089] [EC:2.7.11.22]
106493015  CDC26; cell division cycle 26 [KO:K03359]
106493037  ANAPC2; anaphase promoting complex subunit 2 [KO:K03349]
106493168  [KO:K06639] [EC:3.1.3.16 3.1.3.48]
106493189  ANAPC13; anaphase promoting complex subunit 13 [KO:K12456]
106493331  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
106493490  ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
106493602  PTTG1; pituitary tumor-transforming 1 [KO:K06635]
106493944  CDC16; cell division cycle 16 [KO:K03353]
106494055  TFDP1; transcription factor Dp-1 [KO:K04683]
106494164  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
106494203  BUB3; BUB3, mitotic checkpoint protein [KO:K02180]
106494262  BUB1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
106494356  [KO:K10727]
106494391  MCM4; minichromosome maintenance complex component 4 [KO:K02212] [EC:5.6.2.3]
106494392  PRKDC; protein kinase, DNA-activated, catalytic polypeptide [KO:K06642] [EC:2.7.11.1]
106494747  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
106494814  [KO:K04382] [EC:3.1.3.16]
106494875  SMAD4; SMAD family member 4 [KO:K04501]
106495186  [KO:K11479] [EC:2.7.11.1]
106495275  CUL1; cullin 1 [KO:K03347]
106495393  SMC3; structural maintenance of chromosomes 3 [KO:K06669]
106495739  MAU2; MAU2 sister chromatid cohesion factor [KO:K11266]
106496213  MTBP; MDM2 binding protein [KO:K26116]
106496220  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
106496261  E2F5; E2F transcription factor 5 [KO:K04682]
106496308  RAD21; RAD21 cohesin complex component [KO:K06670]
106496602  E2F1; E2F transcription factor 1 [KO:K17454]
106496690  DBF4B; DBF4 zinc finger B [KO:K06629]
106496904  FBXO5; F-box protein 5 [KO:K10292]
106497137  WEE1; WEE1 G2 checkpoint kinase [KO:K06632] [EC:2.7.11.1]
106497256  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
106497299  TICRR; TOPBP1 interacting checkpoint and replication regulator [KO:K26117]
106497328  YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
106497404  CCNB3; cyclin B3 [KO:K21771]
106497411  HDAC8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
106497413  CDC27; cell division cycle 27 [KO:K03350]
106497650  SMAD2; SMAD family member 2 [KO:K04500]
106497652  [KO:K03352]
106497691  ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
106498229  CCND1; cyclin D1 [KO:K04503]
106498425  MCM6; minichromosome maintenance complex component 6 [KO:K02542] [EC:5.6.2.3]
106498517  ORC4; origin recognition complex subunit 4 [KO:K02606]
106498734  ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
106499348  ANAPC1; anaphase promoting complex subunit 1 [KO:K03348]
106499359  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
106499367  [KO:K06645] [EC:3.1.3.48]
106499449  CDC20; cell division cycle 20 [KO:K03363]
106499493  NIPBL; NIPBL, cohesin loading factor [KO:K06672]
106499538  SKP2; S-phase kinase associated protein 2 [KO:K03875]
106499545  CDC14A; cell division cycle 14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
106499794  CDC7; cell division cycle 7 [KO:K02214] [EC:2.7.11.1]
106499863  WAPL; WAPL cohesin release factor [KO:K25163]
106499916  RBL1; RB transcriptional corepressor like 1 [KO:K04681]
106499960  MAD1L1; MAD1 mitotic arrest deficient like 1 [KO:K06679]
106500151  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
106500154  [KO:K04402]
106500319  E2F3; E2F transcription factor 3 [KO:K06620]
106500372  PDS5B; PDS5 cohesin associated factor B [KO:K11267]
106500420  CCNA1; cyclin A1 [KO:K06627]
106500523  MCM3; minichromosome maintenance complex component 3 [KO:K02541] [EC:5.6.2.3]
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
aam03030  DNA replication
aam04010  MAPK signaling pathway
aam04120  Ubiquitin mediated proteolysis
aam04210  Apoptosis
KO pathway
ko04110   

DBGET integrated database retrieval system