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Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1
University of Southern Denmark.
University of Southern Denmark.
University of Southern Denmark.
University of Southern Denmark.
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2017 (English)In: Cellular and Molecular Life Sciences (CMLS), ISSN 1420-682X, E-ISSN 1420-9071, Vol. 24, p. 4561-4572Article in journal (Refereed) Published
Abstract [en]

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 cellular 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 serine 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 function 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.

Place, publisher, year, edition, pages
2017. Vol. 24, p. 4561-4572
Keywords [en]
HTRA1, MIF, Protein interaction, Yeast-2-hybrid
National Category
Basic Medicine
Identifiers
URN: urn:nbn:se:uu:diva-330365DOI: 10.1007/s00018-017-2592-zISI: 000414150400009PubMedID: 28726057OAI: oai:DiVA.org:uu-330365DiVA, id: diva2:1145269
Funder
Swedish Research Council, M 2006-4268Available from: 2017-09-28 Created: 2017-09-28 Last updated: 2018-02-07Bibliographically approved

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Andersson, Malin

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