γ-Secretase

Supporting information

γ-secretase is a multi-subunit internal protease that cleaves within the transmembrane domain of its substrates. It is an integral membrane protein and minimally consists of four proteins; presenilin, nicastrin, APH-1 and PEN-2. Presenilin is an aspartic protease and the catalytic subunit of the complex.

γ-secretase is involved in the processing of Notch. The Notch receptor is a single transmembrane spanning protein involved in angiogenesis and cell differentiation during embryonic and adult life. Upon ligand binding, the extracellular domain is cleaved by a metalloprotease named TACE. Following this initial cleavage, γ-secretase cleaves within the transmembrane domain of the remaining Notch protein, releasing the intracellular domain (Nβ) into the cytoplasm. Nβ moves to the nucleus where it upregulates transcription of target genes such as Hes1, Hey1 and Hey2. Deficient Notch signaling impairs developmental angiogenesis in the embryo and prevents wound healing in adult tissues.

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Gene Species Gene Symbol Gene Accession No. Protein Accession No.
Presenilin-1 Human PSEN1 NM_000021 P49768
Mouse Psen1 NM_008943 P49769
Rat Psen1 NM_019163 P97887
Presenilin-2 Human PSEN2 NM_000447 P49810
Mouse Psen2 NM_001128605 Q61144
Rat Psen2 NM_031087 O88777
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Literature for γ-Secretase

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis
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Cancer Research Product Guide
Neurodegeneration Product Guide

A collection of over 275 products for neurodegeneration research, the guide includes research tools for the study of:

  • Alzheimer's disease
  • Parkinson's disease
  • Huntington's disease
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Neurodegeneration Product Guide
Alzheimer's Life Science Poster

Written by Alan Palmer and updated in 2015, this poster summarizes structural and functional changes observed in the progression of Alzheimer's disease (AD), as well as classic AD drug targets. The hypotheses behind the neurobiology of AD are discussed alongside the different stages in disease progression. Compounds available from Tocris are listed.

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Alzheimer's Life Science Poster
Angiogenesis Life Science Poster

Written by Yongping Crawford and Napoleone Ferrara, this poster highlights major targets for antiangiogenic therapy, namely tumor- and stromal cell-derived pathways. Intrinsic and acquired resistance are described; antiangiogenic therapies targeting the VEGF pathway are also summarized. Compounds available from Tocris are listed.

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Angiogenesis Life Science Poster

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Cancer Research Product Guide

Cancer Research Product Guide

Our Cancer Research Guide highlights over 750 products for cancer research. Request copy or view PDF today.

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Neurodegeneration Research Product Guide

Neurodegeneration Product Guide

Our Neurodegeneration guide highlights over 275 products for neurodegeneration research. Request copy or view PDF today.

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VEGF Pathway & Anti-Angiogenic Therapy

Written by N. Ferrara & Y. Crawford

Angiogenesis Life Science Poster

A summary of antiangiogenic therapies targeting the VEGF pathway and the mechanisms of therapy resistance. Request copy today.

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Alzheimer's Disease: Neurobiology and Drug Targets

Written by Alan Palmer

Alzheimer's Life Science Poster

Our Alzheimer's disease poster summarizes the structural and functional changes observed in the progression of this neurodegenerative disease. Request copy or view PDF today.

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