Site-1 protease and lysosomal homeostasis.
Biochim Biophys Acta Mol Cell Res
; 1864(11 Pt B): 2162-2168, 2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-28693924
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/ß-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Serina Endopeptidases
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Colesterol
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Pró-Proteína Convertases
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Proteólise
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Mucolipidoses
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Cell Res
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Alemanha