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Table 1.

Involvement of 14-3-3 in human diseases

Isoform Proposed function and comments
Neurological disorders    
   Alzheimer's disease   ζ (β in vitro)   Found in NFTs; binds Tau; interaction with Tau might facilitate aberrant Tau phosphorylation  
   Parkinson's disease   ϵ, γ, ζ, Θ   Found in Lewy bodies; binds α-synuclein; association with α-synuclein might sequester 14-3-3 and inhibit its anti-apoptotic function  
   Spinocerebellar ataxia type 1   ϵ, ζ, η, γ, β   Binds ataxin-1; 14-3-3 binding might stabilize and slow the degredation of pathogenic polyglutamine forms of ataxin-1  
   Miller-Dieker syndrome   ϵ   Gene encoding 14-3-3ϵ is deleted in MDS; loss might result in dephosphorylation of NUDEL, mislocalization of the LISI complex and reduced cytoplasmic dynein function  
   Creutzfeldt-Jakob disease   β, γ, ϵ, η   No function indicated but found in patients' CSF  
Neoplastic disorders    
   Epithelial cancers (breast, gastric, others)   σ   4-3-3σ levels are reduced/absent due to promoter methylation; binds Cdks and p53; participates in G2/M checkpoint control  
   Tuberous sclerosis complex   β, γ, ζ (others?)   Binds TSC2; relieves inhibiton of mTOR signaling by negatively regulating TSC1/TSC2 complex function  
Isoform Proposed function and comments
Neurological disorders    
   Alzheimer's disease   ζ (β in vitro)   Found in NFTs; binds Tau; interaction with Tau might facilitate aberrant Tau phosphorylation  
   Parkinson's disease   ϵ, γ, ζ, Θ   Found in Lewy bodies; binds α-synuclein; association with α-synuclein might sequester 14-3-3 and inhibit its anti-apoptotic function  
   Spinocerebellar ataxia type 1   ϵ, ζ, η, γ, β   Binds ataxin-1; 14-3-3 binding might stabilize and slow the degredation of pathogenic polyglutamine forms of ataxin-1  
   Miller-Dieker syndrome   ϵ   Gene encoding 14-3-3ϵ is deleted in MDS; loss might result in dephosphorylation of NUDEL, mislocalization of the LISI complex and reduced cytoplasmic dynein function  
   Creutzfeldt-Jakob disease   β, γ, ϵ, η   No function indicated but found in patients' CSF  
Neoplastic disorders    
   Epithelial cancers (breast, gastric, others)   σ   4-3-3σ levels are reduced/absent due to promoter methylation; binds Cdks and p53; participates in G2/M checkpoint control  
   Tuberous sclerosis complex   β, γ, ζ (others?)   Binds TSC2; relieves inhibiton of mTOR signaling by negatively regulating TSC1/TSC2 complex function  
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