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Site-1 protease and lysosomal homeostasis
- Source :
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1864:2162-2168
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- The Golgi-resident site-1 protease (S1P) is a key regulator of cholesterol homeostasis and ER stress responses by converting latent transcription factors sterol regulatory element binding proteins (SREPBs) and activating transcription factor 6 (ATF6), as well as viral glycoproteins to their active forms. S1P is also essential for lysosome biogenesis via proteolytic activation of the hexameric GlcNAc-1-phosphotransferase complex required for modification of newly synthesized lysosomal enzymes with the lysosomal targeting signal, mannose 6-phosphate. In the absence of S1P, the catalytically inactive α/β-subunit precursor of GlcNAc-1-phosphotransferase fails to be activated and results in missorting of newly synthesized lysosomal enzymes, and lysosomal accumulation of non-degraded material, which are biochemical features of defective GlcNAc-1-phosphotransferase subunits and the associated pediatric lysosomal diseases mucolipidosis type II and III. The early embryonic death of S1P-deficient mice and the importance of various S1P-regulated biological processes, including lysosomal homeostasis, cautioned for clinical inhibition of S1P. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John.
- Subjects :
- 0301 basic medicine
Proteolysis
Activating transcription factor
Golgi Apparatus
Transferases (Other Substituted Phosphate Groups)
Mannose 6-phosphate
Biology
Mice
03 medical and health sciences
chemistry.chemical_compound
Mucolipidoses
Lysosome
medicine
Animals
Humans
Molecular Biology
Transcription factor
Sterol Regulatory Element Binding Proteins
Mannose 6-phosphate receptor
medicine.diagnostic_test
Serine Endopeptidases
Cell Biology
Endoplasmic Reticulum Stress
Sterol regulatory element-binding protein
Cholesterol
030104 developmental biology
medicine.anatomical_structure
Biochemistry
chemistry
Unfolded protein response
lipids (amino acids, peptides, and proteins)
Proprotein Convertases
Lysosomes
Subjects
Details
- ISSN :
- 01674889
- Volume :
- 1864
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
- Accession number :
- edsair.doi.dedup.....7a0d0809316545f6acee307a6bdd128c