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γ-Secretase: proteasome of the membrane?

Nature Reviews Molecular Cell Biology volume 5, pages 499–504 (2004)Cite this article

Abstract

γ-Secretase — a protease that cleaves within the membrane — was first recognized for its role in the production of amyloidogenic Aβ peptides, but was subsequently found to mediate Notch signalling by releasing the Notch-receptor intracellular domain. Many other γ-secretase substrates have recently been identified, which indicates a broader biological function for this unusual protease. Emerging evidence implies that whereas some intracellular cleavage products of γ-secretase function as signalling molecules, others might simply be intermediates that are destined for degradation.

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Figure 1: The γ-secretase complex and its role in the intramembrane proteolysis of Notch and amyloid precursor protein.
Figure 2: The 26S proteasome and the γ-secretase complex: analogous roles?

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Acknowledgements

We would like to thank the organizers and participants of the Horizon Symposium that triggered this perpective article and, specifically, Bill Parks for reading and commenting on the manuscript.

Author information

Authors and Affiliations

  1. Departments of Molecular Biology and Pharmacology and Medicine, Washington University School of Medicine, St. Louis, 63110, Missouri, USA

    Raphael Kopan & Ma. Xenia G. Ilagan

Authors
  1. Raphael Kopan
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  2. Ma. Xenia G. Ilagan
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Corresponding author

Correspondence to Raphael Kopan.

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The authors declare no competing financial interests.

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Related links

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DATABASES

Flybase

Ci

Swiss-Prot

APP

CD44

DCC

E-cadherin

ERBB4

FE65

F-spondin

Jagged

matrilysin

N-cadherin

Notch

presenilin

S2P

SREBP

syndecan-3

TACE

TIP60

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Kopan, R., Ilagan, M. γ-Secretase: proteasome of the membrane?. Nat Rev Mol Cell Biol 5, 499–504 (2004). https://doi.org/10.1038/nrm1406

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