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Calmodulin regulates MGRN1‐GP78 interaction mediated ubiquitin proteasomal degradation system
- Source :
- UnpayWall, Microsoft Academic Graph
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- The mechanism by which the endoplasmic reticulum (ER) ubiquitin ligases sense stress to potentiate their activity is poorly understood. GP78, an ER E3 ligase, is best known for its role in ER-associated protein degradation, although its activity is also linked to mitophagy, ER-mitochondria junctions, and MAPK signaling, thus highlighting the importance of understanding its regulation. In healthy cells, Mahogunin really interesting new gene (RING) finger 1 (MGRN1) interacts with GP78 and proteasomally degrades it to alleviate mitophagy. Here, we identify calmodulin (CaM) as the adapter protein that senses fluctuating cytosolic Ca2+ levels and modulates the Ca2+-dependent MGRN1-GP78 interactions. When stress elevates cytosolic Ca2+ levels in cultured and primary neuronal cells, CaM binds to both E3 ligases and inhibits their interaction. Molecular docking, simulation, and biophysical studies show that CaM interacts with both proteins with different affinities and binding modes. The physiological impact of this interaction switch manifests in the regulation of ER-associated protein degradation, ER-mitochondria junctions, and relative distribution of smooth ER and rough ER.-Mukherjee, R., Bhattacharya, A., Sau, A., Basu, S., Chakrabarti, S., Chakrabarti, O. Calmodulin regulates MGRN1-GP78 interaction mediated ubiquitin proteasomal degradation system.
- Subjects :
- 0301 basic medicine
Proteasome Endopeptidase Complex
Cell biology
Calmodulin
Ubiquitin-Protein Ligases
Protein degradation
Biochemistry
Mice
03 medical and health sciences
0302 clinical medicine
Endocrinology
Ubiquitin
Mitophagy
Genetics
Animals
Humans
Calcium Signaling
Molecular Biology
Internal medicine
Neurons
biology
Proteasome
Chemistry
Endoplasmic reticulum
Signal transducing adaptor protein
Ubiquitin ligase
Molecular Docking Simulation
Receptors, Autocrine Motility Factor
030104 developmental biology
Proteolysis
biology.protein
Calcium
030217 neurology & neurosurgery
HeLa Cells
Biotechnology
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 33
- Issue :
- 0892-6638
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....6919dc61649a63314f1cdce535f4f584
- Full Text :
- https://doi.org/10.1096/fj.201701413rrr