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PMID:24964035

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Citation

Ueberham, U, Rohn, S, Ueberham, E, Wodischeck, S, Hilbrich, I, Holzer, M, Brückner, MK, Gruschka, H and Arendt, T (2014) Pin1 promotes degradation of Smad proteins and their interaction with phosphorylated tau in Alzheimer's disease. Neuropathol. Appl. Neurobiol. 40:815-32

Abstract

Neurodegeneration in Alzheimer's disease (AD) is characterized by pathological protein aggregates and inadequate activation of cell cycle regulating proteins. Recently, Smad proteins were identified to control the expression of AD relevant proteins such as APP, CDK4 and CDK inhibitors, both critical regulators of cell cycle activation. This might indicate a central role for Smads in AD pathology where they show a substantial deficiency and disturbed subcellular distribution in neurones. Still, the mechanisms driving relocation and decrease of neuronal Smad in AD are not well understood. However, Pin1, a peptidyl-prolyl-cis/trans-isomerase, which allows isomerization of tau protein, was recently identified also controlling the fate of Smads. Here we analyse a possible role of Pin1 for Smad disturbances in AD.

Links

PubMed Online version:10.1111/nan.12163

Keywords

Aged; Aged, 80 and over; Alzheimer Disease/metabolism; Female; Hippocampus/metabolism; Humans; Male; Middle Aged; NIMA-Interacting Peptidylprolyl Isomerase; Peptidylprolyl Isomerase/metabolism; Phosphorylation; Proteolysis; Smad Proteins/metabolism; tau Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SMAD3

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q8BUN5

F

  • has_input:(UniProtKB:Q13526)
  • occurs_at:(SO:0000170)

Seeded From UniProt

complete

HUMAN:PIN1

involved_in

GO:0001932: regulation of protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:Q15796)

Seeded From UniProt

complete

HUMAN:PIN1

involved_in

GO:0032092: positive regulation of protein binding

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:Q15796)
  • has_input:(UniProtKB:P10636)

Seeded From UniProt

complete

HUMAN:PIN1

involved_in

GO:0010468: regulation of gene expression

ECO:0000314: direct assay evidence used in manual assertion

P

  • regulates_expression_of:(UniProtKB:Q15796)

Seeded From UniProt

complete

HUMAN:PIN1

enables

GO:0003755: peptidyl-prolyl cis-trans isomerase activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:SMAD2

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q62432

F

  • has_input:(UniProtKB:Q13526)
  • occurs_at:(SO:0000170)

Seeded From UniProt

complete

MOUSE:SMAD2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SMAD2

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SMAD2

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000353: physical interaction evidence used in manual assertion

ENSEMBL_GeneID:ENSG00000127445

F

  • has_input:(UniProtKB:Q9QUR7)
  • occurs_at:(SO:0000170)

Seeded From UniProt

complete

MOUSE:SMAD3

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000353: physical interaction evidence used in manual assertion

ENSEMBL_GeneID:ENSG00000127445

F

  • has_input:(UniProtKB:Q9QUR7)
  • occurs_at:(SO:0000170)

Seeded From UniProt

complete

HUMAN:SMAD2

enables

GO:0048156: tau protein binding

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q62432

F

Seeded From UniProt

complete

HUMAN:SMAD2

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q62432

F

  • has_input:(ENSEMBL:ENSG00000127445)
  • occurs_at:(SO:0000170)

Seeded From UniProt

complete

HUMAN:SMAD3

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q8BUN5

F

  • has_input:(ENSEMBL:ENSG00000127445)
  • occurs_at:(SO:0000170)

Seeded From UniProt

complete

HUMAN:PIN1

involved_in

GO:0032092: positive regulation of protein binding

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_regulation_target:(UniProtKB:Q15796)
  • has_regulation_target:(UniProtKB:P10636)

Seeded From UniProt

complete

HUMAN:PIN1

involved_in

GO:0001932: regulation of protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

has_regulation_target:(UniProtKB:Q15796)

Seeded From UniProt

complete

HUMAN:PIN1

involved_in

GO:0010468: regulation of gene expression

ECO:0000314: direct assay evidence used in manual assertion

P

regulates_expression_of:(ENSEMBL:ENSG00000175387)

Seeded From UniProt

complete

MOUSE:SMAD2

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SMAD2

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SMAD2

enables

GO:0048156: tau protein binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:SMAD2

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000353: physical interaction evidence used in manual assertion

ENSEMBL_GeneID:ENSG00000127445

F

  • has_input:(ENSEMBL:ENSMUSG00000032171)
  • occurs_at:(SO:0000170)

Seeded From UniProt

complete

MOUSE:SMAD3

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000353: physical interaction evidence used in manual assertion

ENSEMBL_GeneID:ENSG00000127445

F

  • has_input:(ENSEMBL:ENSMUSG00000032171)
  • occurs_at:(SO:0000170)

Seeded From UniProt

complete

Notes

See also

References

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