Hydrophobicity of the C-terminal GPI-anchor Attachment Signals Determines ER-associated Degradation Pathway of Precursor Proteins
10.13865/j.cnki.cjbmb.2022.09.1154
- Author:
Nan ZHANG
1
;
Yi-Shi LIU
1
;
Fujita MORIHISA
1
;
Xiao-Dong GAO
1
Author Information
1. Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University
- Publication Type:Journal Article
- Keywords:
endoplasmic reticulum-associated degradation (ERAD);
glycosylphosphatidylinositol anchored protein (GPI-anchored protein);
protein hydrophobicity
- From:
Chinese Journal of Biochemistry and Molecular Biology
2022;38(10):1351-1358
- CountryChina
- Language:Chinese
-
Abstract:
More than 150 glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are expressed in mammalian cells and involved in various physiological processes such as immune recognition, cell communication and signal transduction. GPI is transferred to proteins in the endoplasmic reticulum (ER). When GPI-anchoring is impaired, precursor proteins are thought to be degraded through ER-associated degradation (ERAD). However, the mechanism of their degradation in ERAD remains unclear. To investigate the impact of ERAD pathways on degradation of GPI precursor proteins, we used series of knockout (KO) human embryonic kidney 293 (HEK293) cells defective in PIGS gene, which encodes a GPI transamidase complex subunit, combined with KO in HRD1 (PIGS-HRD1-KO) or GP78 (PIGSGP78-KO), which encodes the E3 ubiquitin ligases for the ERAD pathways. We compared the stability of 16 GPI precursor proteins in the ERAD-deficient cells with the parental PIGS-KO cells. Western blotting data showed that the GPI precursor proteins were stabilized in either PIGS-HRD1-KO (I
