Eukaryotic DING Proteins Are Endogenous: An Immunohistological Study in Mouse Tissues

Jean-Marc Collombet,Mikael Elias,Aurélie Joffre,Guillaume Gotthard,Eric Chabrière,Frédérique Renault,Dominique Baubichon,Elise Four,Daniel Rochu,Art J Lustig

doi:10.1371/journal.pone.0009099

Jean-Marc Collombet, Mikael Elias + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0009099

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Abstract

BackgroundDING proteins encompass an intriguing protein family first characterized by their conserved N-terminal sequences. Some of these proteins seem to have key roles in various human diseases, e.g., rheumatoid arthritis, atherosclerosis, HIV suppression. Although this protein family seems to be ubiquitous in eukaryotes, their genes are consistently lacking from genomic databases. Such a lack has considerably hampered functional studies and has fostered therefore the hypothesis that DING proteins isolated from eukaryotes were in fact prokaryotic contaminants.Principal FindingsIn the framework of our study, we have performed a comprehensive immunological detection of DING proteins in mice. We demonstrate that DING proteins are present in all tissues tested as isoforms of various molecular weights (MWs). Their intracellular localization is tissue-dependant, being exclusively nuclear in neurons, but cytoplasmic and nuclear in other tissues. We also provide evidence that germ-free mouse plasma contains as much DING protein as wild-type.SignificanceHence, data herein provide a valuable basis for future investigations aimed at eukaryotic DING proteins, revealing that these proteins seem ubiquitous in mouse tissue. Our results strongly suggest that mouse DING proteins are endogenous. Moreover, the determination in this study of the precise cellular localization of DING proteins constitute a precious evidence to understand their molecular involvements in their related human diseases.

Highlights

DING proteins, named according to their four conserved Nterminal amino-acid residues, encompass a recently discovered protein family [1]
Eukaryotic DING genes are consistently missing from genomic databases proteins belonging to this family seem to be ubiquitous in eukaryotes: they have been identified in animals, plants (Hypericum perforatum, Arabidopsis thaliana, potato, tobacco) and fungi (Candida albicans, Ganoderma lucidum) [2,3] mostly as a 40 kDa protein or higher molecular weight DING proteins [4]
Other bands between 52 and 140 kDa are more likely high molecular weight DING proteins (HMW-DING) comparable to the ones already observed in plants [4]

Summary

Introduction

DING proteins, named according to their four conserved Nterminal amino-acid residues, encompass a recently discovered protein family [1]. No complete eukaryotic DING coding sequence is available in databases, few partial DNA sequences have been either cloned [3] or identified in non-annoted parts of genomes [2]. These few pieces of sequences show that DING proteins are strongly conserved [2]. DING proteins encompass an intriguing protein family first characterized by their conserved N-terminal sequences Some of these proteins seem to have key roles in various human diseases, e.g., rheumatoid arthritis, atherosclerosis, HIV suppression. This protein family seems to be ubiquitous in eukaryotes, their genes are consistently lacking from genomic databases. Such a lack has considerably hampered functional studies and has fostered the hypothesis that DING proteins isolated from eukaryotes were prokaryotic contaminants

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