PXD005218

PXD005218 is an original dataset announced via ProteomeXchange.

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	2020-07-24
AnnouncementXML	Submission_2020-07-23_22:45:59.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

Revision	Datetime	Status	ChangeLog Entry
0	2016-10-25 00:11:31	ID requested
⏵ 1	2020-07-23 22:46:00	announced

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]

curator keyword: Biological

submitter keyword: BiP/ GRP78, HYOU1/ GRP170, Marinesco-Sjögren syndrome, co-chaperone, chaperonopathy, neuroprotection

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD005218

PRIDE project URI

• PRIDE
  1. PXD005218
     1. Label: PRIDE project
     2. Name: Tracking effects of SIL1 increase: taking a closer look beyond the consequences of elevated expression level