PXD005218 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Tracking effects of SIL1 increase: taking a closer look beyond the consequences of elevated expression level |
Description | SIL1 acts as a co-chaperone for the major ER-resident chaperone BiP and thus plays a role in many BiP-dependent cellular functions such as protein folding control and unfolded protein response. Whereas increase of BiP upon cellular stress conditions is a well-known phenomenon, elevation of SIL1 under stress conditions was thus far solely studied in yeast and different studies indicated an adverse effect of SIL1 increase. This is seemingly in contrast with the beneficial effect of SIL1 increase in surviving neurons in neurodegenerative disorders such as Amyotrophic Lateral Sclerosis and Alzheimer disease. In the present study, we systematically addressed these controversial findings. Using cell biological, morphological and biochemical methods, we could demonstrate that that SIL1 is increased in various mammalian cells and neuronal tissues upon induction of cellular stress. Investigation of heterozygous SIL1/Sil1 mutant cells and tissues supported this finding. Moreover, SIL1 protein was found to be stabilized during ER stress. Increased SIL1 initiates ER stress in a concentration-dependent manner which is in accordance with the described adverse effect of increased SIL1. However, our results also suggest that protective levels are achieved by the secretion of excessive SIL1 and GRP170 (no longer perturbing ER homeostasis) and that moderately increased SIL1 also ameliorates cellular fitness under stress conditions. Results of our immunoprecipitation studies indicate that under cellular stress conditions SIL1 might act in a BiP-independent manner. Unbiased proteomic studies revealed that elevated SIL1 levels alter the expression of several proteins including crucial players in neurodegeneration, especially in Alzheimer disease. This finding is in accordance with our observation of increased SIL1-immunoreactivity in surviving neurons of Alzheimer disease autopsy cases and supports the assumption that SIL1 plays a protective role in neurodegenerative disorders. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:09:43.738.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Laxmikanth Kollipara |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2016-10-25 00:11:31 | ID requested | |
1 | 2020-07-23 22:46:00 | announced | |
⏵ 2 | 2024-10-22 05:09:51 | announced | 2024-10-22: Updated project metadata. |
Publication List
10.1007/s12035-017-0494-6; |
Labisch T, Buchkremer S, Phan V, Kollipara L, Gatz C, Lentz C, Nolte K, Vervoorts J, Coraspe JAG, Sickmann A, Carr S, Zahedi RP, Weis J, Roos A, Tracking Effects of SIL1 Increase: Taking a Closer Look Beyond the Consequences of Elevated Expression Level. Mol Neurobiol, 55(3):2524-2546(2018) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: BiP/ GRP78, HYOU1/ GRP170, Marinesco-Sjögren syndrome, co-chaperone, chaperonopathy, neuroprotection |
Contact List
Dr. René P Zahedi |
contact affiliation | Group Leader Protein Dynamics Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V. Otto-Hahn-Straße 6b 44227 Dortmund, Germany |
contact email | rene.zahedi@isas.de |
lab head | |
Laxmikanth Kollipara |
contact affiliation | Leibniz – Institut für Analytische Wissenschaften - ISAS - e.V. |
contact email | laxmikanth.kollipara@isas.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD005218
- Label: PRIDE project
- Name: Tracking effects of SIL1 increase: taking a closer look beyond the consequences of elevated expression level