PXD023433

PXD023433 is an original dataset announced via ProteomeXchange.

Title	Stress-induced tyrosine phosphorylation of RtcB modulates IRE1 activity and signaling outputs.
Description	Endoplasmic Reticulum (ER) stress is a hallmark of various diseases, which is dealt with through the activation of an adaptive signaling pathway named the Unfolded Protein Response (UPR). This response is mediated by three ER-resident sensors and the most evolutionary conserved, IRE1α signals through its cytosolic kinase and endoribonuclease (RNase) activities. IRE1α RNase activity can either catalyze the initial step of XBP1 mRNA unconventional splicing or degrade a number of RNAs through Regulated IRE1-Dependent Decay (RIDD). The balance between these two activities plays an instrumental role in cells’ life and death decisions upon ER stress. Until now, the biochemical and biological outputs of IRE1α RNase activity have been well documented, however, the precise mechanisms controlling whether IRE1 signaling is adaptive or pro-death (terminal) remain unclear. This prompted us to further investigate those mechanisms and we hypothesized that XBP1 mRNA splicing and RIDD activity could be co-regulated by the IRE1α RNase regulatory network. We showed that a key nexus in this pathway is the tRNA ligase RtcB which, together with IRE1α, is responsible for XBP1 mRNA splicing. We demonstrated that RtcB is tyrosine phosphorylated by c-Abl and dephosphorylated by PTP1B. Moreover, we identified RtcB Y306 as a key residue which, when phosphorylated, perturbs RtcB interaction with IRE1α, thereby attenuating XBP1 mRNA splicing and favoring RIDD. Our results demonstrate that the IRE1α RNase regulatory network is dynamically fine-tuned by tyrosine kinases and phosphatases upon various stresses and that the nature of the stress determines cell adaptive or death outputs.
HostingRepository	PRIDE
AnnounceDate	2022-02-21
AnnouncementXML	Submission_2022-02-21_10:07:31.578.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Luc Negroni
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-06 01:45:34	ID requested
⏵ 1	2022-02-21 10:07:32	announced

Dataset with its publication pending

submitter keyword: Endoplasmic Reticulum, UPR, XBP1s

Eric Chevet
contact affiliation	Centre Eugène Marquis - INSERM U1242, University of Rennes, France
contact email	eric.chevet1@gmail.com
lab head
Luc Negroni
contact affiliation	CNRS
contact email	luc.negroni@igbmc.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023433
     1. Label: PRIDE project
     2. Name: Stress-induced tyrosine phosphorylation of RtcB modulates IRE1 activity and signaling outputs.