KEGG   PATHWAY: lruf04110
Entry
lruf04110                   Pathway                                
Name
Cell cycle - Lynx rufus (bobcat)
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
lruf04110  Cell cycle
lruf04110

Other DBs
GO: 0000278
Organism
Lynx rufus (bobcat) [GN:lruf]
Gene
124506147  G1/S-specific cyclin-D1 [KO:K04503]
124501054  G1/S-specific cyclin-D2 [KO:K10151]
124528816  G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
124501159  cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
124523204  cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
124512196  retinoblastoma-associated protein isoform X1 [KO:K06618]
124503708  retinoblastoma-like protein 1 isoform X1 [KO:K04681]
124511315  retinoblastoma-like protein 2 isoform X1 [KO:K16332]
124525633  tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
124528271  histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
124514885  histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
124503500  transcription factor E2F1 [KO:K17454]
124515072  transcription factor E2F2 isoform X1 [KO:K09389]
124528848  transcription factor E2F3 isoform X1 [KO:K06620]
124511388  transcription factor E2F4 [KO:K04682]
124507747  transcription factor E2F5 isoform X1 [KO:K04682]
124513984  transcription factor Dp-1 isoform X1 [KO:K04683]
124526297  transcription factor Dp-2 isoform X1 [KO:K09392]
124526728  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
124511094  transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
124510378  transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
124512625  transforming growth factor beta-3 proprotein [KO:K13377]
124517096  mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
124508465  mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
124516988  mothers against decapentaplegic homolog 4 isoform X1 [KO:K04501]
124507805  myc proto-oncogene protein [KO:K04377]
124514675  zinc finger and BTB domain-containing protein 17 [KO:K10500]
124525759  cyclin-dependent kinase inhibitor 2A-like isoform X1 [KO:K06621]
124501072  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
124516229  cyclin-dependent kinase 4 inhibitor C [KO:K06622]
124524296  cyclin-dependent kinase 4 inhibitor D [KO:K06623]
124500999  cyclin-dependent kinase inhibitor 1B [KO:K06624]
124506120  cyclin-dependent kinase inhibitor 1C-like [KO:K09993]
124528296  cyclin-dependent kinase inhibitor 1 [KO:K06625]
124511276  G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
124518951  G1/S-specific cyclin-E2 [KO:K06626]
124502320  cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
124515676  S-phase kinase-associated protein 1 [KO:K03094]
124524656  cullin-1 [KO:K03347]
124501699  E3 ubiquitin-protein ligase RBX1 [KO:K03868] [EC:2.3.2.32]
124522217  S-phase kinase-associated protein 2 [KO:K03875]
124520480  cyclin-A2 [KO:K06627]
124509481  cyclin-A1 [KO:K06627]
124513341  cell division control protein 6 homolog [KO:K02213]
124511889  DNA replication factor Cdt1-like [KO:K10727]
124515948  origin recognition complex subunit 1-like [KO:K02603]
124515431  origin recognition complex subunit 2 isoform X1 [KO:K02604]
124528673  origin recognition complex subunit 3 isoform X1 [KO:K02605]
124515256  origin recognition complex subunit 4 isoform X1 [KO:K02606]
124523988  origin recognition complex subunit 5 [KO:K02607]
124511283  origin recognition complex subunit 6 isoform X1 [KO:K02608]
124524662  DNA replication licensing factor MCM2 [KO:K02540] [EC:5.6.2.3]
124528546  DNA replication licensing factor MCM3 [KO:K02541] [EC:5.6.2.3]
124507636  DNA replication licensing factor MCM4 [KO:K02212] [EC:5.6.2.3]
124502173  DNA replication licensing factor MCM5 [KO:K02209] [EC:5.6.2.3]
124515885  DNA replication licensing factor MCM6 [KO:K02542] [EC:5.6.2.3]
124519202  DNA replication licensing factor MCM7 isoform X1 [KO:K02210] [EC:5.6.2.3]
124525708  cell division control protein 45 homolog [KO:K06628]
124517314  treslin-like isoform X1 [KO:K26117]
124507560  mdm2-binding protein [KO:K26116]
124515743  cell division cycle 7-related protein kinase isoform X1 [KO:K02214] [EC:2.7.11.1]
124522065  protein DBF4 homolog B-like [KO:K06629]
124524276  protein DBF4 homolog A-like isoform X1 [KO:K06629]
124506828  cyclin-dependent kinase 1 isoform X1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
124507726  LOW QUALITY PROTEIN: cyclin-dependent kinase 1-like [KO:K02087] [EC:2.7.11.22 2.7.11.23]
124502384  G2/mitotic-specific cyclin-B1 [KO:K05868]
124508045  G2/mitotic-specific cyclin-B2 [KO:K21770]
124509542  G2/mitotic-specific cyclin-B3-like [KO:K21771]
124503343  M-phase inducer phosphatase 2 isoform X1 [KO:K05866] [EC:3.1.3.48]
124516125  M-phase inducer phosphatase 3-like [KO:K05867] [EC:3.1.3.48]
124503145  14-3-3 protein beta/alpha [KO:K16197]
124503513  14-3-3 protein theta [KO:K16197]
124518954  14-3-3 protein zeta/delta [KO:K16197]
124512264  LOW QUALITY PROTEIN: 14-3-3 protein theta-like [KO:K16197]
124517052  14-3-3 protein zeta/delta-like [KO:K16197]
124512972  14-3-3 protein epsilon isoform X1 [KO:K06630]
124501900  14-3-3 protein epsilon-like [KO:K06630]
124518269  14-3-3 protein eta [KO:K16198]
124519118  14-3-3 protein gamma [KO:K16198]
124517768  serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
124505599  wee1-like protein kinase isoform X1 [KO:K06632] [EC:2.7.11.1]
124522873  wee1-like protein kinase 2 [KO:K06632] [EC:2.7.11.1]
124517777  membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase isoform X1 [KO:K06633] [EC:2.7.11.1]
124518806  cyclin-H isoform X1 [KO:K06634]
124517869  cyclin-dependent kinase 7 isoform X1 [KO:K02202] [EC:2.7.11.22 2.7.11.23]
124503517  anaphase-promoting complex subunit 1 [KO:K03348]
124522396  anaphase-promoting complex subunit 2 [KO:K03349]
124513558  cell division cycle protein 27 homolog isoform X1 [KO:K03350]
124520599  anaphase-promoting complex subunit 4 [KO:K03351]
124518394  anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
124514035  cell division cycle protein 16 homolog isoform X1 [KO:K03353]
124518304  anaphase-promoting complex subunit 7 [KO:K03354]
124516099  cell division cycle protein 23 homolog [KO:K03355]
124520962  anaphase-promoting complex subunit 10 isoform X1 [KO:K03357]
124503246  anaphase-promoting complex subunit CDC26 isoform X1 [KO:K03359]
124526338  anaphase-promoting complex subunit 13 [KO:K12456]
124505329  anaphase-promoting complex subunit 15 isoform X1 [KO:K25228]
124506890  anaphase-promoting complex subunit 16 isoform X1 [KO:K25229]
124514669  cell division cycle protein 20 homolog isoform X1 [KO:K03363]
124509126  LOW QUALITY PROTEIN: cell division cycle protein 20 homolog [KO:K03363]
124507069  securin-like isoform X1 [KO:K06635]
124515405  securin-like [KO:K06635]
124508736  securin-like isoform X1 [KO:K06635]
124502024  separin-like [KO:K02365] [EC:3.4.22.49]
124501057  structural maintenance of chromosomes protein 1B isoform X1 [KO:K06636]
124522304  structural maintenance of chromosomes protein 1A isoform X1 [KO:K06636]
124507136  structural maintenance of chromosomes protein 3 [KO:K06669]
124507768  double-strand-break repair protein rad21 homolog [KO:K06670]
124527085  cohesin subunit SA-1 [KO:K06671]
124513902  cohesin subunit SA-2 isoform X1 [KO:K06671]
124509543  transcriptional regulator ATRX isoform X1 [KO:K10779]
124502355  putative ATP-dependent RNA helicase DDX11-like protein 8 [KO:K11273] [EC:5.6.2.7]
124522141  nipped-B-like protein isoform X1 [KO:K06672]
124524971  MAU2 chromatid cohesion factor homolog isoform X1 [KO:K11266]
124521560  histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
124517558  N-acetyltransferase ESCO1 [KO:K11268] [EC:2.3.1.-]
124521012  N-acetyltransferase ESCO2-like [KO:K11268] [EC:2.3.1.-]
124511459  sister chromatid cohesion protein PDS5 homolog B isoform X1 [KO:K11267]
124519992  sister chromatid cohesion protein PDS5 homolog A [KO:K11267]
124506947  wings apart-like protein homolog isoform X1 [KO:K25163]
124504861  sororin-like [KO:K17390]
124519526  aurora kinase B isoform X1 [KO:K11479] [EC:2.7.11.1]
124526867  shugoshin 1-like [KO:K11580]
124520278  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
124515685  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
124510821  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
124504617  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
124510105  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
124512134  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
124512512  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
124505607  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
124528074  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
124517650  kinetochore protein NDC80 homolog [KO:K11547]
124508705  kinetochore scaffold 1-like [KO:K11542]
124528615  dual specificity protein kinase TTK-like [KO:K08866] [EC:2.7.12.1]
124519155  mitotic spindle assembly checkpoint protein MAD1-like isoform X1 [KO:K06679]
124520996  mitotic spindle assembly checkpoint protein MAD2A [KO:K02537]
124515096  mitotic spindle assembly checkpoint protein MAD2B [KO:K13728]
124508713  mitotic checkpoint serine/threonine-protein kinase BUB1 beta [KO:K06637] [EC:2.7.11.1]
124507204  mitotic checkpoint protein BUB3 isoform X1 [KO:K02180]
124504244  mitotic checkpoint serine/threonine-protein kinase BUB1-like [KO:K02178] [EC:2.7.11.1]
124522777  pachytene checkpoint protein 2 homolog [KO:K22399]
124528205  MAD2L1-binding protein isoform X1 [KO:K26093]
124522924  fizzy-related protein homolog isoform X1 [KO:K03364]
124528224  F-box only protein 5-like isoform X1 [KO:K10292]
124515237  dual specificity protein phosphatase CDC14A isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
124529313  dual specificity protein phosphatase CDC14B-like isoform X1 [KO:K06639] [EC:3.1.3.16 3.1.3.48]
124517735  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
124501617  histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
124507635  DNA-dependent protein kinase catalytic subunit [KO:K06642] [EC:2.7.11.1]
124526514  serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
124504822  serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
124501378  E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
124519563  cellular tumor antigen p53 isoform X1 [KO:K04451]
124524872  growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
124515398  growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
124523614  growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
124503991  proliferating cell nuclear antigen [KO:K04802]
124516591  14-3-3 protein sigma [KO:K06644]
124505184  serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
124518366  serine/threonine-protein kinase Chk2-like isoform X1 [KO:K06641] [EC:2.7.11.1]
124523955  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.
  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
lruf03030  DNA replication
lruf04010  MAPK signaling pathway
lruf04120  Ubiquitin mediated proteolysis
lruf04210  Apoptosis
KO pathway
ko04110   
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