Evidence map›Paper›PMID 31462935›Full record

ArticleMobile DNA2019

A human endogenous retrovirus encoded protease potentially cleaves numerous cellular proteins.

Giuseppe Rigogliuso, Martin L Biniossek, John L Goodier, Bettina Mayer, Gavin C Pereira, Oliver Schilling, Eckart Meese, Jens Mayer

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Mobile DNA, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.5field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 10 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Giuseppe Rigogliuso1Department of Human Genetics, Medical Faculty, University of Saarland, Homburg, Germany.
Martin L Biniossek2Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany.
John L Goodier3McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD USA.
Bettina Mayer2Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany.
Gavin C Pereira3McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD USA.
Oliver Schilling4Institute of Surgical Pathology, Medical Center, University of Freiburg, Freiburg, Germany.
Eckart Meese1Department of Human Genetics, Medical Faculty, University of Saarland, Homburg, Germany.
Jens Mayer1Department of Human Genetics, Medical Faculty, University of Saarland, Homburg, Germany.ORCID 0000-0002-1090-5765
Saarland University · DEUniversity of Freiburg · DEJohns Hopkins University · US

Funding

Retrotransposition independent LINE 1-induced DNA damage in normal and aging cellsR21AG056840 · NIA · JOHNS HOPKINS UNIVERSITY · PI GOODIER, JOHN LAWRENCE · 2018 to 2019
$450k
A role for endogenous retroelements in Aicardi-Goutieres SyndromeR21HD083915 · NICHD · JOHNS HOPKINS UNIVERSITY · PI GOODIER, JOHN LAWRENCE · 2016 to 2017
$449k
NIA NIH HHS R21 AG056840NICHD NIH HHS R21 HD083915
6 · The paper itself

Abstract

backgroundA considerable portion of the human genome derives from retroviruses inherited over millions of years. Human endogenous retroviruses (HERVs) are usually severely mutated, yet some coding-competent HERVs exist. The HERV-K(HML-2) group includes evolutionarily young proviruses that encode typical retroviral proteins. HERV-K(HML-2) has been implicated in various human diseases because transcription is often upregulated and some of its encoded proteins are known to affect cell biology. HERV-K(HML-2) Protease (Pro) has received little attention so far, although it is expressed in some disease contexts and other retroviral proteases are known to process cellular proteins.

resultsWe set out to identify human cellular proteins that are substrates of HERV-K(HML-2) Pro employing a modified Terminal Amine Isotopic Labeling of Substrates (TAILS) procedure. Thousands of human proteins were identified by this assay as significantly processed by HERV-K(HML-2) Pro at both acidic and neutral pH. We confirmed cleavage of a majority of selected human proteins in vitro and in co-expression experiments in vivo. Sizes of processing products observed for some of the tested proteins coincided with product sizes predicted by TAILS. Processed proteins locate to various cellular compartments and participate in diverse, often disease-relevant cellular processes. A limited number of HERV-K(HML-2) reference and non-reference loci appears capable of encoding active Pro.

conclusionsOur findings from an approach combining TAILS with experimental verification of candidate proteins in vitro and in cultured cells suggest that hundreds of cellular proteins are potential substrates of HERV-K(HML-2) Pro. It is therefore conceivable that even low-level expression of HERV-K(HML-2) Pro affects levels of a diverse array of proteins and thus has a functional impact on cell biology and possible relevance for human diseases. Further studies are indicated to elucidate effects of HERV-K(HML-2) Pro expression regarding human substrate proteins, cell biology, and disease. The latter also calls for studies on expression of specific HERV-K(HML-2) loci capable of encoding active Pro. Endogenous retrovirus-encoded Pro activity may also be relevant for disease development in species other than human.

Indexed as

Endogenous retrovirusHERV-KPathogenesisProteolysisRetrotransposonRetroviral protease

Identifiers

PMID31462935
PMCPMC6707001
OpenAlexW2969284701

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.