Proteomics

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A human endogenous retrovirus encoded protease potentially cleaves numerous cellular proteins


ABSTRACT: Background: The human genome consists of considerable portions derived from retroviruses inherited for millions of years. So-called 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 still encode typical retroviral proteins. HERV-K(HML-2) has been implicated in various human diseases because transcription is often upregulated and some of the encoded proteins are known to affect cell biology. HERV-K(HML-2) Protease (Pro) has received little attention so far, although it appears expressed in some disease contexts and other retroviral proteases are known to process cellular proteins. Results: We set out to identify human cellular proteins being substrates of HERV-K(HML-2) Pro employing a modified Terminal Amine Isotopic Labeling of Substrates (TAILS) procedure. Thousands of human proteins were identified as significantly processed by HERV-K(HML-2) Pro. Identified proteins locate to various cellular compartments and participate in diverse, often disease-relevant cellular processes. We verified cleavage of a majority of selected human proteins in vitro and in vivo. Conclusions: Hundreds, if not thousands of cellular proteins are potential substrates of HERV-K(HML-2) Pro. It is conceivable that even low-level expression of HERV-K(HML-2) Pro has a functional impact on cell biology and thus relevance for human diseases. Specific studies will be required to elucidate effects of HERV-K(HML-2) Pro expression regarding human substrate proteins, cell biology and disease. Endogenous retrovirus-encoded Pro activity may also be relevant for disease development in species other than human.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Oliver Schilling  

LAB HEAD: Oliver Schilling

PROVIDER: PXD013296 | Pride | 2019-09-02

REPOSITORIES: Pride

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

Rigogliuso Giuseppe G   Biniossek Martin L ML   Goodier John L JL   Mayer Bettina B   Pereira Gavin C GC   Schilling Oliver O   Meese Eckart E   Mayer Jens J  

Mobile DNA 20190822


<h4>Background</h4>A 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 biol  ...[more]

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