Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1

Åsa Fex Svenningsen*, Svenja Loering, Anna Lahn Sørensen, Ha Uyen Buu Huynh, Simone Hjæresen, Nellie Anne Martin, Jesper Bonnet Møller, Maria Louise Elkjær, Uffe Holmskov, Zsolt Illés, Malin Andersson, Solveig Beck Nielsen, Eirikur Benedikz

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cel-lular level. It is upregulated in neurodegenerative diseases and cancer although its function is far from clear. Here, we report the finding of a new binding partner to MIF, the ser-ine protease HTRA1. This enzyme cleaves several growth factors, extracellular matrix molecules and is implicated in some of the same diseases as MIF. We show that the func-tion of the binding between MIF and HTRA1 is to inhibit the proteolytic activity of HTRA1, modulating the availability of molecules that can change cell growth and differentiation. MIF is therefore the first endogenous inhibitor ever found for HTRA1. It was found that both molecules were present in astrocytes and that the functional binding has the ability to modulate astrocytic activities important in development and disease of the CNS.
Original languageEnglish
JournalCellular and Molecular Life Sciences
Volume74
Issue number24
Pages (from-to)4561–4572
ISSN1420-682X
DOIs
Publication statusPublished - 2017

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Macrophage Migration-Inhibitory Factors
Central Nervous System Diseases
Neurodegenerative Diseases
Peptide Hydrolases
Central Nervous System
Enzymes
Growth
Neoplasms
Proteins

Keywords

  • MIF
  • HTRA1
  • Protein Interaction
  • Yeast-2-Hybrid
  • Yeast-2-hybrid
  • Protein interaction

Cite this

@article{a5107b355b2f4b79a26904345cc53d78,
title = "Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1",
abstract = "Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cel-lular level. It is upregulated in neurodegenerative diseases and cancer although its function is far from clear. Here, we report the finding of a new binding partner to MIF, the ser-ine protease HTRA1. This enzyme cleaves several growth factors, extracellular matrix molecules and is implicated in some of the same diseases as MIF. We show that the func-tion of the binding between MIF and HTRA1 is to inhibit the proteolytic activity of HTRA1, modulating the availability of molecules that can change cell growth and differentiation. MIF is therefore the first endogenous inhibitor ever found for HTRA1. It was found that both molecules were present in astrocytes and that the functional binding has the ability to modulate astrocytic activities important in development and disease of the CNS.",
keywords = "MIF, HTRA1, Protein Interaction, Yeast-2-Hybrid, Yeast-2-hybrid, Protein interaction",
author = "{Fex Svenningsen}, {\AA}sa and Svenja Loering and S{\o}rensen, {Anna Lahn} and {Uyen Buu Huynh}, Ha and Simone Hj{\ae}resen and Martin, {Nellie Anne} and M{\o}ller, {Jesper Bonnet} and Elkj{\ae}r, {Maria Louise} and Uffe Holmskov and Zsolt Ill{\'e}s and Malin Andersson and Nielsen, {Solveig Beck} and Eirikur Benedikz",
year = "2017",
doi = "10.1007/s00018-017-2592-z",
language = "English",
volume = "74",
pages = "4561–4572",
journal = "Cellular and Molecular Life Sciences",
issn = "1420-682X",
publisher = "Springer",
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Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1. / Fex Svenningsen, Åsa; Loering, Svenja; Sørensen, Anna Lahn; Uyen Buu Huynh, Ha; Hjæresen, Simone; Martin, Nellie Anne; Møller, Jesper Bonnet; Elkjær, Maria Louise; Holmskov, Uffe; Illés, Zsolt; Andersson, Malin; Nielsen, Solveig Beck; Benedikz, Eirikur.

In: Cellular and Molecular Life Sciences, Vol. 74, No. 24, 2017, p. 4561–4572.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1

AU - Fex Svenningsen, Åsa

AU - Loering, Svenja

AU - Sørensen, Anna Lahn

AU - Uyen Buu Huynh, Ha

AU - Hjæresen, Simone

AU - Martin, Nellie Anne

AU - Møller, Jesper Bonnet

AU - Elkjær, Maria Louise

AU - Holmskov, Uffe

AU - Illés, Zsolt

AU - Andersson, Malin

AU - Nielsen, Solveig Beck

AU - Benedikz, Eirikur

PY - 2017

Y1 - 2017

N2 - Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cel-lular level. It is upregulated in neurodegenerative diseases and cancer although its function is far from clear. Here, we report the finding of a new binding partner to MIF, the ser-ine protease HTRA1. This enzyme cleaves several growth factors, extracellular matrix molecules and is implicated in some of the same diseases as MIF. We show that the func-tion of the binding between MIF and HTRA1 is to inhibit the proteolytic activity of HTRA1, modulating the availability of molecules that can change cell growth and differentiation. MIF is therefore the first endogenous inhibitor ever found for HTRA1. It was found that both molecules were present in astrocytes and that the functional binding has the ability to modulate astrocytic activities important in development and disease of the CNS.

AB - Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cel-lular level. It is upregulated in neurodegenerative diseases and cancer although its function is far from clear. Here, we report the finding of a new binding partner to MIF, the ser-ine protease HTRA1. This enzyme cleaves several growth factors, extracellular matrix molecules and is implicated in some of the same diseases as MIF. We show that the func-tion of the binding between MIF and HTRA1 is to inhibit the proteolytic activity of HTRA1, modulating the availability of molecules that can change cell growth and differentiation. MIF is therefore the first endogenous inhibitor ever found for HTRA1. It was found that both molecules were present in astrocytes and that the functional binding has the ability to modulate astrocytic activities important in development and disease of the CNS.

KW - MIF

KW - HTRA1

KW - Protein Interaction

KW - Yeast-2-Hybrid

KW - Yeast-2-hybrid

KW - Protein interaction

U2 - 10.1007/s00018-017-2592-z

DO - 10.1007/s00018-017-2592-z

M3 - Journal article

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VL - 74

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JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

SN - 1420-682X

IS - 24

ER -