PXD055838-1

PXD055838 is an original dataset announced via ProteomeXchange.

Title	Identification of RNA binding proteins associated with the 5'UTR of Nrf2 during oxidative stress
Description	Nrf2 transcript factor plays an important role in cellular defense against oxidative stress due to its control for the expression of antioxidant and detoxification genes. We have found that Nrf2 undergoes de novo protein translation when mammalian cells encounter oxidative stress. Here, we report the discovery of DHX9 as a binding protein for Nrf2 5’UTR. H2O2 treatment causes dose- or time- dependent increases of DHX9 binding to Nrf2 5’UTR, in parallel with elevation of Nrf2 protein. Inhibiting DHX9 expression with siRNA or its activity with YK-4-279 blocked H2O2 from inducing Nrf2 mRNA recruitment to the ribosomes or Nrf2 protein elevation. As a nuclear protein, DHX9 was found to increase its abundance in the cytosol with oxidative stress. An increase of DHX9 was detected in total ribosomal collections in cells treated with H2O2, most significantly with 100 uM H2O2, and at 60 mins. Ribosomal fractionation revealed an increase of DHX9 protein at 43/48S and 80S fractions in H2O2 treated cells. H2O2 treatment caused an RNA dependent increase of DHX9 interaction with eIF3 The binding of DHX9 to Nrf2 5’UTR probe was enhanced by H2O2 treated cells or by deducting the length of Nrf2 5’UTR, suggesting a negative element normally prohibiting DHX9 binding to Nrf2 5’UTR. RNase digestion enhanced DHX9 association with the ribosomes. Our data have revealed a novel mechanism of de novo Nrf2 protein translation under oxidative stress involving DHX9 binding to Nrf2 5’UTR, perhaps via removal of a negative RNA element, to recruit 43S pre-initiation complex for translation initiation.
HostingRepository	PRIDE
AnnounceDate	2025-06-23
AnnouncementXML	Submission_2025-06-22_16:13:04.305.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD055838
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Daniel Wurm
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-13 01:45:05	ID requested
⏵ 1	2025-06-22 16:13:05	announced

10.6019/PXD055838;

10.1016/j.mcpro.2025.100977;

Dai W, Diao H, Qu H, Wurm D, Lu Y, Chen QM, DExH-Box Helicase 9 Participates in De Novo Nrf2 Protein Translation Under Oxidative Stress. Mol Cell Proteomics, 24(6):100977(2025) [pubmed]

submitter keyword: Oxidative stress, affinity proteomics, Nrf2, Proteomics, RNA binding proteins

Qin Chen
contact affiliation	R. Ken Coit College of Pharmacy, Department of Pharmacy Practice & Science, The University of Arizona
contact email	qchen@arizona.edu
lab head
Daniel Wurm
contact affiliation	University of Arizona
contact email	wurm@arizona.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055838
     1. Label: PRIDE project
     2. Name: Identification of RNA binding proteins associated with the 5'UTR of Nrf2 during oxidative stress