Proteomic profiling of γ-secretase substrates and mapping of substrate requirements
2008

Profiling γ-Secretase Substrates

Sample size: 2500 publication 10 minutes Evidence: moderate

Author Information

Author(s): Hemming Matthew L, Elias Joshua E, Gygi Steven P, Selkoe Dennis J

Primary Institution: Brigham and Women's Hospital and Harvard Medical School

Hypothesis

What are the substrates of γ-secretase and what determines their cleavage?

Conclusion

The study identified a small population of new γ-secretase substrates, all of which are type I transmembrane proteins with specific domain requirements for cleavage.

Supporting Evidence

  • All identified substrates were type I transmembrane proteins.
  • Specific domains were required for γ-secretase cleavage.
  • At least two mechanisms for substrate targeting were identified.

Takeaway

This study found that a special enzyme called γ-secretase can cut certain proteins in our cells, but only if they have the right parts to be cut.

Methodology

An unbiased proteomic screen using SILAC and mass spectrometry was performed to identify γ-secretase substrates.

Limitations

The study was limited to a specific cell line (HeLa) and may not represent all possible γ-secretase substrates in different cell types.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pbio.0060257

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