Reactome | p16INK4A mutants do not bind CDK4,CDK6

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p16INK4A mutants do not bind CDK4,CDK6 Show undefined attributes

authored	[InstanceEdit:9632937] Orlic-Milacic, Marija, 2018-12-24
category	transition
compartment	[Compartment:70101] cytosol
created	[InstanceEdit:9630793] Orlic-Milacic, Marija, 2018-12-03
dbId	9630795
disease	[Disease:1500689] cancer
displayName	p16INK4A mutants do not bind CDK4,CDK6
entityFunctionalStatus	[EntityFunctionalStatus:9630819] loss_of_function of p16INK4A LoF mutants (CDK4/6) [cytosol]
eventOf	[Pathway:R-HSA-9630794] Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 - Homo sapiens [Pathway:R-HSA-9632700] Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 - Homo sapiens
input	[DefinedSet:R-HSA-69209] CDK4,CDK6 [cytosol] [CandidateSet:R-HSA-9630804] p16INK4A LoF mutants (CDK4/6) [cytosol]
isChimeric	false
isInDisease	true
isInferred	false
literatureReference	[LiteratureReference:9630820] A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6 [LiteratureReference:9630869] Germline mutations of the CDKN2 gene in UK melanoma families [LiteratureReference:9631144] CDKN2A unclassified variants in familial malignant melanoma: combining functional and computational approaches for their assessment [LiteratureReference:9631243] Predicting functional significance of cancer-associated p16(INK4a) mutations in CDKN2A [LiteratureReference:9631247] Functional reassessment of P16 variants using a transfection-based assay [LiteratureReference:9632347] Biologic and biochemical analyses of p16(INK4a) mutations from primary tumors [LiteratureReference:9632507] Functional evaluation of tumour-specific variants of p16INK4a/CDKN2A: correlation with protein structure information [LiteratureReference:9632601] C-terminal domain of p16(INK4a) is adequate in inducing cell cycle arrest, growth inhibition and CDK4/6 interaction similar to the full length protein in HT-1080 fibrosarcoma cells [LiteratureReference:9630871] Functional impairment of melanoma-associated p16(INK4a) mutants in melanoma cells despite retention of cyclin-dependent kinase 4 binding [LiteratureReference:9631273] Functional, structural, and genetic evaluation of 20 CDKN2A germ line mutations identified in melanoma-prone families or patients [LiteratureReference:9632578] CDKN2A/p16 is inactivated in most melanoma cell lines [LiteratureReference:9649227] Loss of heterozygosity at chromosome 9p21 (INK4-p14ARF locus): homozygous deletions and mutations in the p16 and p14ARF genes in sporadic primary melanomas [LiteratureReference:9649202] A cell cycle regulator potentially involved in genesis of many tumor types [LiteratureReference:9649229] High frequency of p16INK4A gene alterations in hepatocellular carcinoma [LiteratureReference:9646518] COSMIC: somatic cancer genetics at high-resolution
modified	[InstanceEdit:9830342] Matthews, Lisa, 2023-03-08
name	p16INK4A mutants do not bind CDK4,CDK6
normalReaction	[Reaction:R-HSA-182594] Association of INK4 family proteins with CDK4/6
releaseDate	2019-06-12
reviewStatus	[ReviewStatus:9821382] five stars
reviewed	[InstanceEdit:9645278] Bennett, Dorothy C, 2019-04-23 [InstanceEdit:9649238] Nathan, Vaishnavi, 2019-06-03 [InstanceEdit:9649237] Hayward, Nicholas K, 2019-06-03
schemaClass	FailedReaction
species	[Species:48887] Homo sapiens
stId	R-HSA-9630795
summation	[Summation:9630823] Wild type p16INK4A is able to form a complex with either CDK...

Referrals

(hasEvent)

[Pathway:R-HSA-9630794] Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6
[Pathway:R-HSA-9632700] Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6

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