KEGG   PATHWAY: hgl04110
Entry
hgl04110                    Pathway                                
Name
Cell cycle - Heterocephalus glaber (naked mole-rat)
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
hgl04110  Cell cycle
hgl04110

Other DBs
GO: 0000278
Organism
Heterocephalus glaber (naked mole-rat) [GN:hgl]
Gene
101712621  Ccnd1; cyclin D1 [KO:K04503]
101721480  Ccnd2; cyclin D2 [KO:K10151]
101708062  Ccnd3; cyclin D3 [KO:K10152]
101702608  Cdk4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
101719908  Cdk6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
101703701  Rb1; RB transcriptional corepressor 1 [KO:K06618]
101707342  Rbl1; RB transcriptional corepressor like 1 [KO:K04681]
101701252  Rbl2; RB transcriptional corepressor like 2 [KO:K16332]
101724428  Abl1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
101715102  Hdac1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
101712029  Hdac2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
101717980  E2f1; E2F transcription factor 1 [KO:K17454]
101711793  E2f2; E2F transcription factor 2 [KO:K09389]
101698963  E2f3; E2F transcription factor 3 [KO:K06620]
101716696  E2f4; E2F transcription factor 4 [KO:K04682]
101701212  E2f5; E2F transcription factor 5 [KO:K04682]
101720935  Tfdp1; transcription factor Dp-1 [KO:K04683]
101698510  Tfdp2; transcription factor Dp-2 [KO:K09392]
101701301  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
101704230  Tgfb1; transforming growth factor beta 1 [KO:K13375]
101707457  Tgfb2; transforming growth factor beta 2 [KO:K13376]
101712904  Tgfb3; transforming growth factor beta 3 [KO:K13377]
101714203  Smad2; SMAD family member 2 [KO:K04500]
101713378  Smad3; SMAD family member 3 [KO:K23605]
101703764  Smad4; SMAD family member 4 [KO:K04501]
101704740  Myc; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
101710815  Zbtb17; zinc finger and BTB domain containing 17 [KO:K10500]
101701062  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
101721834  Cdkn2c; cyclin dependent kinase inhibitor 2C [KO:K06622]
101720531  Cdkn2d; cyclin dependent kinase inhibitor 2D [KO:K06623]
101698721  Cdkn1b; cyclin dependent kinase inhibitor 1B [KO:K06624]
101726530  Cdkn1c; cyclin dependent kinase inhibitor 1C [KO:K09993]
101710552  Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625]
101701725  Ccne2; cyclin E2 [KO:K06626]
101711961  Ccne1; cyclin E1 [KO:K06626]
101725353  Cdk2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
101704606  Skp1; S-phase kinase associated protein 1 [KO:K03094]
101703786  Cul1; cullin 1 [KO:K03347]
101712475  Rbx1; ring-box 1 [KO:K03868] [EC:2.3.2.32]
101706248  Skp2; S-phase kinase associated protein 2 [KO:K03875]
101717784  Ccna2; cyclin A2 [KO:K06627]
101718933  Ccna1; cyclin A1 [KO:K06627]
101724964  Cdc6; cell division cycle 6 [KO:K02213]
101714018  Cdt1; chromatin licensing and DNA replication factor 1 [KO:K10727]
101713340  Orc1; origin recognition complex subunit 1 [KO:K02603]
101717321  Orc2; origin recognition complex subunit 2 [KO:K02604]
101700236  Orc3; origin recognition complex subunit 3 [KO:K02605]
101707950  Orc4; origin recognition complex subunit 4 [KO:K02606]
101718856  Orc5; origin recognition complex subunit 5 [KO:K02607]
101697513  Orc6; origin recognition complex subunit 6 [KO:K02608]
106007526  DNA replication licensing factor MCM2-like [KO:K02540] [EC:5.6.2.3]
101711827  DNA replication licensing factor MCM2-like [KO:K02540] [EC:5.6.2.3]
101719015  Mcm3; minichromosome maintenance complex component 3 [KO:K02541] [EC:5.6.2.3]
101721409  Mcm4; minichromosome maintenance complex component 4 [KO:K02212] [EC:5.6.2.3]
101708511  Mcm5; minichromosome maintenance complex component 5 [KO:K02209] [EC:5.6.2.3]
101698140  Mcm6; minichromosome maintenance complex component 6 [KO:K02542] [EC:5.6.2.3]
101724967  Mcm7; minichromosome maintenance complex component 7 [KO:K02210] [EC:5.6.2.3]
101714952  Cdc45; cell division cycle 45 [KO:K06628]
101703037  Ticrr; TOPBP1 interacting checkpoint and replication regulator [KO:K26117]
101714982  Mtbp; MDM2 binding protein [KO:K26116]
101720948  Cdc7; cell division cycle 7 [KO:K02214] [EC:2.7.11.1]
101706943  Dbf4; DBF4 zinc finger [KO:K06629]
101718846  Cdk1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
101712597  cyclin-dependent kinase 1-like [KO:K02087] [EC:2.7.11.22 2.7.11.23]
101700598  G2/mitotic-specific cyclin-B1-like [KO:K05868]
101719153  Ccnb1; cyclin B1 [KO:K05868]
101696424  Ccnb2; cyclin B2 [KO:K21770]
101706141  Ccnb3; cyclin B3 [KO:K21771]
101701077  Cdc25b; cell division cycle 25B [KO:K05866] [EC:3.1.3.48]
101712931  Cdc25c; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
101720841  14-3-3 protein zeta/delta [KO:K16197]
101720117  Ywhaq; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
101721954  Ywhaz; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
101705080  Ywhab; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
101717238  Ywhae; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
101716439  Ywhag; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
101709704  Ywhah; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
101712650  14-3-3 protein eta [KO:K16198]
101721399  Plk1; polo like kinase 1 [KO:K06631] [EC:2.7.11.21]
101706756  Wee2; WEE1 homolog 2 [KO:K06632] [EC:2.7.11.1]
101704354  Wee1; WEE1 G2 checkpoint kinase [KO:K06632] [EC:2.7.11.1]
101702827  wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
101721451  Pkmyt1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
101714118  Ccnh; cyclin H [KO:K06634]
101702664  Cdk7; cyclin dependent kinase 7 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
101720524  Anapc1; anaphase promoting complex subunit 1 [KO:K03348]
101719594  Anapc2; anaphase promoting complex subunit 2 [KO:K03349]
101717421  Cdc27; cell division cycle 27 [KO:K03350]
101699443  Anapc4; anaphase promoting complex subunit 4 [KO:K03351]
101724399  Anapc5; anaphase promoting complex subunit 5 [KO:K03352]
101724017  Cdc16; cell division cycle 16 [KO:K03353]
101720262  Anapc7; anaphase promoting complex subunit 7 [KO:K03354]
101711746  Cdc23; cell division cycle 23 [KO:K03355]
101724776  Anapc10; anaphase promoting complex subunit 10 [KO:K03357]
101713652  Anapc11; anaphase promoting complex subunit 11 [KO:K03358]
101705159  Cdc26; cell division cycle 26 [KO:K03359]
101724802  Anapc13; anaphase promoting complex subunit 13 [KO:K12456]
101699532  Anapc15; anaphase promoting complex subunit 15 [KO:K25228]
101725384  Anapc16; anaphase promoting complex subunit 16 [KO:K25229]
101707229  Cdc20; cell division cycle 20 [KO:K03363]
101723041  Pttg1; pituitary tumor-transforming 1 [KO:K06635]
101723260  Espl1; extra spindle pole bodies like 1, separase [KO:K02365] [EC:3.4.22.49]
101700152  Smc1b; structural maintenance of chromosomes 1B [KO:K06636]
101713253  Smc1a; structural maintenance of chromosomes 1A [KO:K06636]
101725969  Smc3; structural maintenance of chromosomes 3 [KO:K06669]
101705536  Rad21; RAD21 cohesin complex component [KO:K06670]
101698509  Stag1; stromal antigen 1 [KO:K06671]
101716438  Stag2; stromal antigen 2 [KO:K06671]
101705766  Atrx; ATRX, chromatin remodeler [KO:K10779]
101721808  Ddx11; DEAD/H-box helicase 11 [KO:K11273] [EC:5.6.2.7]
101702533  Nipbl; NIPBL, cohesin loading factor [KO:K06672]
101716510  Mau2; MAU2 sister chromatid cohesion factor [KO:K11266]
101697998  Hdac8; histone deacetylase 8 [KO:K11405] [EC:3.5.1.98]
101720068  Esco2; establishment of sister chromatid cohesion N-acetyltransferase 2 [KO:K11268] [EC:2.3.1.-]
101718018  Esco1; establishment of sister chromatid cohesion N-acetyltransferase 1 [KO:K11268] [EC:2.3.1.-]
101706850  Pds5a; PDS5 cohesin associated factor A [KO:K11267]
101725183  Pds5b; PDS5 cohesin associated factor B [KO:K11267]
101702640  Wapl; WAPL cohesin release factor [KO:K25163]
101701382  Cdca5; cell division cycle associated 5 [KO:K17390]
101713391  Aurkb; aurora kinase B [KO:K11479] [EC:2.7.11.1]
101698945  Sgo1; shugoshin 1 [KO:K11580]
101707511  Ppp2ca; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
101726191  Ppp2cb; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
101722244  Ppp2r1b; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
101703470  Ppp2r1a; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
101726315  Ppp2r5c; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
101711583  Ppp2r5e; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
101724057  Ppp2r5d; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
101706140  Ppp2r5b; protein phosphatase 2 regulatory subunit B'beta [KO:K11584]
101712512  Ppp2r5a; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
101704930  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform-like [KO:K11584]
101724914  Ndc80; NDC80, kinetochore complex component [KO:K11547]
101715049  Knl1; kinetochore scaffold 1 [KO:K11542]
101702153  Ttk; TTK protein kinase [KO:K08866] [EC:2.7.12.1]
101711604  Mad1l1; MAD1 mitotic arrest deficient like 1 [KO:K06679]
101721329  Mad2l2; MAD2 mitotic arrest deficient-like 2 (yeast) [KO:K13728]
101705847  Bub1b; BUB1 mitotic checkpoint serine/threonine kinase B [KO:K06637] [EC:2.7.11.1]
101697549  Bub3; BUB3, mitotic checkpoint protein [KO:K02180]
101724275  Bub1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
101702860  Trip13; thyroid hormone receptor interactor 13 [KO:K22399]
101708522  Mad2l1bp; MAD2L1 binding protein [KO:K26093]
101697340  Fzr1; fizzy/cell division cycle 20 related 1 [KO:K03364]
101713387  Fbxo5; F-box protein 5 [KO:K10292]
101713083  Cdc14b; cell division cycle 14B [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101724071  Cdc14a; cell division cycle 14A [KO:K06639] [EC:3.1.3.16 3.1.3.48]
101711512  Ep300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
101714025  Crebbp; CREB binding protein [KO:K04498] [EC:2.3.1.48]
101722248  Prkdc; protein kinase, DNA-activated, catalytic polypeptide [KO:K06642] [EC:2.7.11.1]
101701996  Atr; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
101718948  Atm; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
101724821  Mdm2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
101701769  Tp53; tumor protein p53 [KO:K04451]
101725746  Gadd45a; growth arrest and DNA damage inducible alpha [KO:K04402]
101711314  Gadd45g; growth arrest and DNA damage inducible gamma [KO:K04402]
101710909  Gadd45b; growth arrest and DNA damage inducible beta [KO:K04402]
101714005  Pcna; proliferating cell nuclear antigen [KO:K04802]
101719248  Sfn; stratifin [KO:K06644]
101701035  Chek1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
101721212  Chek2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
101699133  Cdc25a; cell division cycle 25A [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
hgl03030  DNA replication
hgl04010  MAPK signaling pathway
hgl04120  Ubiquitin mediated proteolysis
hgl04210  Apoptosis
KO pathway
ko04110   

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Genome (1)   
   KEGG GENOME (1)   
Gene (160)   
   KEGG GENES (160)   
All databases (161)   

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