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Membrane protein secretases

N M Hooper1, E H Karran, A J Turner

  • 1Department of Biochemistry and Molecular Biology, University of Leeds, U.K.

The Biochemical Journal
|January 15, 1997
PubMed
Summary
This summary is machine-generated.

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Membrane proteins are cleaved by secretases into soluble forms, impacting cell signaling and disease. These secretases, potentially metallosecretases, offer new therapeutic targets for neurodegeneration and inflammation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Many Type 1 or Type II membrane proteins exist as soluble, circulating forms.
  • These soluble proteins are generated through proteolysis by enzymes called secretases or sheddases.
  • This process releases physiologically active proteins and down-regulates cell surface protein levels.

Purpose of the Study:

  • To review current knowledge of secretases involved in membrane protein shedding.
  • To compare various secretases and their characteristics.
  • To outline strategies for developing cell-free assays for secretase purification and cloning.

Main Methods:

  • Review of existing literature on secretases and their substrates.
  • Comparison of known secretase properties, including inhibitor sensitivity and activators.

Related Experiment Videos

  • Discussion of methods for in vitro secretase activity assessment.

    • Main Results:

    • Secretases cleave membrane proteins near the extracellular face, releasing active soluble forms.
    • Examples include Alzheimer's amyloid precursor protein, angiotensin converting enzyme, and TNF superfamily members.
    • Secretases share features like metalloprotease inhibitor sensitivity and phorbol ester upregulation, suggesting a metallosecretase family.

    Conclusions:

    • Secretases play crucial roles in regulating cell surface proteins and are implicated in diseases like neurodegeneration, apoptosis, oncogenesis, and inflammation.
    • The common characteristics of secretases point towards a conserved metallosecretase family.
    • Further characterization and purification of secretases are essential for developing novel therapeutic strategies.