NDLI: La Autoantigen Mediates Oxidant Induced De Novo Nrf2 Protein Translation

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zhang, Jack Dinh, Thai Nho Kappeler, Kyle Tsaprailis, George Chen, Qin M.
Description	Country affiliation: United States Author Affiliation: Zhang J ( Department of Pharmacology, University of Arizona, College of Medicine, 1501 N Campbell Ave, Tucson, Arizona 85724, USA.)
Abstract	Nrf2 gene encodes a transcription factor that regulates the expression of a cluster of antioxidant and detoxification genes. Recent works from our laboratory indicate that oxidative stress causes rapid de novo synthesis of Nrf2 protein. We have found that 5' Untranslated Region (5'UTR) of Nrf2 allows the mRNA to undergo an Internal Ribosomal Entry Site (IRES) mediated protein translation. Using liquid chromatography tandem MS, we have discovered that La/SSB protein bound to Nrf2 5'UTR in response to oxidative stress. In vitro RNA binding and in vivo ribonucleoprotein immunoprecipitation showed H(2)O(2) dose and time dependent increases of La/SSB binding to Nrf2 5'UTR. La/SSB protein translocated from the nuclei to cytoplasm and distributed in the perinuclear space in cells treated with H(2)O(2). Isolation of ribosomal fractions indicated that oxidants caused an association of La/SSB with ribosomes. Physical interaction of La/SSB with representative proteins from the small or large subunits of ribosomes was found to increase in cells responding to H(2)O(2) treatment. Knocking down La/SSB gene with siRNA prevented Nrf2 protein elevation or Nrf2 5'UTR activation by oxidants. In contrast, overexpression of La/SSB gene was able to enhance Nrf2 5'UTR activation and Nrf2 protein increase. Our data suggest that oxidants cause nuclear export of La/SSB protein and subsequent association of La/SSB with Nrf2 5'UTR and ribosomes. These events contribute to de novo Nrf2 protein translation because of oxidative stress.
File Format	HTM / HTML
ISSN	15359476
e-ISSN	15359484
DOI	10.1074/mcp.M111.015032
Journal	Molecular & Cellular Proteomics
Issue Number	6
Volume Number	11
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2012-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Proteomics Autoantigens Metabolism Hydrogen Peroxide Pharmacology Nf-e2-related Factor 2 Oxidants Phosphoproteins Protein Biosynthesis 5' Untranslated Regions Active Transport, Cell Nucleus Amino Acid Sequence Physiology Fatty Acids, Unsaturated Gene Expression Regulation Hela Cells Karyopherins Antagonists & Inhibitors Molecular Sequence Data Genetics Oxidative Stress Protein Binding Receptors, Cytoplasmic And Nuclear Ribosomal Proteins Ribosome Subunits, Small, Eukaryotic Transcription, Genetic Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Medicine Analytical Chemistry Molecular Biology Biochemistry

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La Autoantigen Mediates Oxidant Induced De Novo Nrf2 Protein Translation*

Distinct cytoplasmic maturation steps of 40S ribosomal subunit precursors require hRio2

Driving ribosome assembly

IRES-induced conformational changes in the ribosome and the mechanism of translation initiation by internal ribosomal entry.

Functional dichotomy of ribosomal proteins during the synthesis of mammalian 40S ribosomal subunits

Biochemical and functional analysis of a 9-nt RNA sequence that affects translation efficiency in eukaryotic cells.

Regulation of Nuclear Import and Export of Negative Cofactor 2

Properties of the ribosomal P2 protein autoantigen are similar to those of foreign protein antigens.

Preferential utilization of Imp7/8 in nuclear import of Smads.

La Autoantigen Mediates Oxidant Induced De Novo Nrf2 Protein Translation

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La Autoantigen Mediates Oxidant Induced De Novo Nrf2 Protein Translation*

Distinct cytoplasmic maturation steps of 40S ribosomal subunit precursors require hRio2

Driving ribosome assembly

IRES-induced conformational changes in the ribosome and the mechanism of translation initiation by internal ribosomal entry.

Functional dichotomy of ribosomal proteins during the synthesis of mammalian 40S ribosomal subunits

Biochemical and functional analysis of a 9-nt RNA sequence that affects translation efficiency in eukaryotic cells.

Regulation of Nuclear Import and Export of Negative Cofactor 2

Properties of the ribosomal P2 protein autoantigen are similar to those of foreign protein antigens.

Preferential utilization of Imp7/8 in nuclear import of Smads.

La Autoantigen Mediates Oxidant Induced De Novo Nrf2 Protein Translation