PXD017887-2

PXD017887 is an original dataset announced via ProteomeXchange.

Title	Identification of heat induced, RNF4 regulated ubiquitylation sites
Description	Exposure of cells to heat or oxidative stress causes misfolding of proteins. To avoid toxic protein aggregation, cells have evolved nuclear and cytosolic protein quality control (PQC) systems. In response to proteotoxic stress cells also limit protein synthesis by triggering transient storage of mRNAs and RNA binding proteins (RBPs) in cytosolic stress granules (SGs). We demonstrate that the SUMO-targeted ubiquitin ligase (StUbL) pathway, which is part of the nuclear proteostasis network, regulates SG dynamics. We provide evidence that inactivation of SUMO deconjugases under proteotoxic stress initiates SUMO-primed, RNF4-dependent ubiquitylation of RBPs that typically condense into SGs. Impairment of SUMO-primed ubiquitylation drastically delays SG resolution upon stress release. Importantly, the StUbL system regulates compartmentalization of an amyotrophic lateral sclerosis (ALS)-associated mutant of FUS in SGs. We propose that the StUbL system functions as surveillance pathway for aggregation-prone RBPs in the nucleus thereby linking the nuclear and cytosolic axis of proteotoxic stress response. Toidentify heat induced, RNF4 regulated ubiquitylation sites we performed an unbiased SILAC-based mass-spectrometry screen comparing heat-induced ubiquitylation in control and RNF4 depleted cells.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_06:58:29.754.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jan Keiten-Schmitz
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-04 23:55:11	ID requested
1	2023-06-30 01:53:48	announced
⏵ 2	2023-11-14 06:58:30	announced	2023-11-14: Updated project metadata.
3	2024-10-22 05:51:32	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Ubiquitylation heatshock RNF4 HeLa

Stefan Müller
contact affiliation	Institute of Biochemistry II, Goethe University, Medical School, Frankfurt, Germany
contact email	ste.mueller@em.uni-frankfurt.de
lab head
Jan Keiten-Schmitz
contact affiliation	Goethe University, Frankfurt am Main, Germany
contact email	keiten-schmitz@em.uni-frankfurt.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017887
     1. Label: PRIDE project
     2. Name: Identification of heat induced, RNF4 regulated ubiquitylation sites