Reactome | Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes

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Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes Show undefined attributes

authored	[InstanceEdit:113706] Matthews, L, 2004-06-19 02:00:00
catalystActivity	[CatalystActivity:182511] cyclin-dependent protein serine/threonine kinase activity of p-T172-CDK4,p-T177-CDK6:CCND:CDKN1A,CDKN1B,(CDKN1C); p-T172-CDK4,p-T177-CDK6:CCND; (p-T172-CDK4,p-T177-CDK6:CCND:p-Y88-CDKN1B) [nucleoplasm]
catalystActivityReference	[CatalystActivityReference:9643320] cyclin-dependent protein serine/threonine kinase activity of p-T172-CDK4,p-T177-CDK6:CCND:CDKN1A,CDKN1B,(CDKN1C); p-T172-CDK4,p-T177-CDK6:CCND; (p-T172-CDK4,p-T177-CDK6:CCND:p-Y88-CDKN1B) [nucleoplasm] Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation
category	transition
compartment	[Compartment:7660] nucleoplasm
dbId	69227
displayName	Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes
edited	[InstanceEdit:9689364] Orlic-Milacic, Marija, 2020-05-18
eventOf	[Pathway:R-HSA-69231] Cyclin D associated events in G1 - Homo sapiens
figure	[Figure:69228] /figures/Cdk46_RbP.jpg
followingEvent	[Pathway:R-HSA-69205] G1/S-Specific Transcription - Homo sapiens [Reaction:R-HSA-8961888] E2F1 binds the CCNA1 gene promoter - Homo sapiens [Reaction:R-HSA-8961636] E2F1 binds the POLA1 gene promoter - Homo sapiens [Reaction:R-HSA-8961946] E2F1 binds the CDT1 gene promoter - Homo sapiens [Reaction:R-HSA-8961688] E2F1 binds the FBXO5 gene promoter - Homo sapiens [Reaction:R-HSA-8961991] E2F1 binds the TK1 gene promoter - Homo sapiens [Reaction:R-HSA-8961863] E2F1 binds the DHFR gene promoter - Homo sapiens [BlackBoxEvent:R-HSA-8962050] TYMS gene expression - Homo sapiens [Reaction:R-HSA-8961671] E2F1 binds the ORC1 gene promoter - Homo sapiens [Reaction:R-HSA-8961972] E2F1 binds the RRM2 gene promoter - Homo sapiens [Reaction:R-HSA-4331324] E2F1 binds BBC3 (PUMA) promoter - Homo sapiens [Reaction:R-HSA-4331327] E2F1 binds PMAIP1 (NOXA) promoter - Homo sapiens [Reaction:R-HSA-8961840] E2F1 binds the CCNE1 gene promoter - Homo sapiens [Reaction:R-HSA-8961961] E2F1 binds the CDC25A gene promoter - Homo sapiens [Reaction:R-HSA-8961907] E2F1 binds the CDC45 gene promoter - Homo sapiens [Reaction:R-HSA-8961620] E2F1 binds the CDC6 gene promoter - Homo sapiens [Reaction:R-HSA-8961651] E2F1 binds the PCNA gene promoter - Homo sapiens [Reaction:R-HSA-8961920] E2F1 binds the CDK1 gene promoter - Homo sapiens [Reaction:R-HSA-3209096] E2F1, E2F2, or E2F3 and SP1 bind p14ARF promoter - Homo sapiens [Reaction:R-HSA-113503] PP2A mediated localization of RB1 protein in chromatin - Homo sapiens [Reaction:R-HSA-188386] Association of Rb with Cyclin E:Cdk2 complexes - Homo sapiens
input	[SimpleEntity:R-ALL-29358] ATP [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-68642] RB1 [nucleoplasm]
isInDisease	false
isInferred	false
literatureReference	[LiteratureReference:113709] Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation [LiteratureReference:9687301] Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes [LiteratureReference:9687300] Cumulative effect of phosphorylation of pRB on regulation of E2F activity [LiteratureReference:9687329] Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1 [LiteratureReference:9687325] Downregulation of cyclin D1 alters cdk 4- and cdk 2-specific phosphorylation of retinoblastoma protein [LiteratureReference:9687293] Differential regulation of retinoblastoma tumor suppressor protein by G(1) cyclin-dependent kinase complexes in vivo [LiteratureReference:9687305] Transient Hysteresis in CDK4/6 Activity Underlies Passage of the Restriction Point in G1 [LiteratureReference:9687327] Cyclin D activates the Rb tumor suppressor by mono-phosphorylation [LiteratureReference:9687302] A Code of Mono-phosphorylation Modulates the Function of RB
modified	[InstanceEdit:10560457] Wright, Adam, 2024-03-07
name	Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes
orthologousEvent	[Reaction:R-MMU-69227] Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes - Mus musculus [Reaction:R-RNO-69227] Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes - Rattus norvegicus [Reaction:R-CFA-69227] Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes - Canis familiaris [Reaction:R-BTA-69227] Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes - Bos taurus [Reaction:R-SSC-69227] Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes - Sus scrofa [Reaction:R-DRE-69227] Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes - Danio rerio [Reaction:R-XTR-69227] Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes - Xenopus tropicalis [Reaction:R-GGA-69227] Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes - Gallus gallus
output	[SimpleEntity:R-ALL-113582] ADP [nucleoplasm] [DefinedSet:R-HSA-9687348] monophosphorylated RB1 [nucleoplasm]
precedingEvent	[Reaction:R-HSA-8942836] CDK4/6:CCND complexes are activated by T-loop phosphorylation of CDK4/6 - Homo sapiens [BlackBoxEvent:R-HSA-9659820] RB1 translocates to the nucleus - Homo sapiens
previousReviewStatus	[ReviewStatus:9821384] two stars
regulatedBy	[NegativeRegulation:9757606] Negative regulation by 'p-T172-CDK4:CCND:CDK4 inhibitors [nucleoplasm]' [NegativeRegulation:9757607] Negative regulation by 'p-T177-CDK6:CCND:CDK6 inhibitors [nucleoplasm]'
releaseDate	2004-07-06
reviewStatus	[ReviewStatus:9821385] four stars
reviewed	[InstanceEdit:9689366] Dick, Frederick Andrew, 2020-05-17 [InstanceEdit:9757975] Kadambat Nair, Sisira, 2021-11-02
revised	[InstanceEdit:9687445] Orlic-Milacic, Marija, 2020-05-07
schemaClass	Reaction
species	[Species:48887] Homo sapiens
stId	R-HSA-69227
summation	[Summation:213349] CDK4 and CDK6, in complex with D type cyclins (CCND1, CCND2 ...

Referrals

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(hasEvent)

[Pathway:R-HSA-69231] Cyclin D associated events in G1

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