Extracellular Vesicle-Associated Moonlighting Proteins: Heat Shock Proteins and Metalloproteinases
Protein moonlighting has been defined as one protein that plays multiple roles. Intracellular heat shock proteins (HSP) are originally molecular chaperones that assist in the folding of intracellular proteins, whereas extracellular HSP plays a cytokine-li
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Abstract Introduction Protein moonlighting has been defined as one protein that plays multiple roles. Intracellular heat shock proteins (HSP) are originally molecular chaperones that assist in the folding of intracellular proteins, whereas extracellular HSP plays a cytokine-like role through binding to receptors expressed on the surface of immune and cancer cells. On the other hand, matrix metalloproteinases (MMP) are originally extracellular proteinases, whereas intracellular MMP alters transcription and gene expression. In here, we therefore propose to define HSP and MMP as moonlight proteins and find these moonlighting proteins in extracellular vesicles (EV), which carry and mediate molecular transfer of the cargo factors from the producer cells to the recipient cells. Methods PubMed and Google databases were searched with keywords including “moonlight proteins, protein moonlighting, HSP, MMP, extracellular vesicles, exosomes, alarmin, danger- or damage-associated molecular patterns (DAMPs). Results Many members of HSP and MMP protein families are overexpressed and extracellularly released in cancers and inflammatory diseases, including rheumatoid
Authors Takanori Eguchi and Eman Ahmed Taha have equally contributed to this chapter. T. Eguchi (*) Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan e-mail: [email protected]; [email protected] E. A. Taha Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt © Springer Nature Switzerland AG 2020 A. A. A. Asea, P. Kaur (eds.), Heat Shock Proteins, https://doi.org/10.1007/7515_2020_25
T. Eguchi and E. A. Taha
arthritis (RA). HSP are also known as alarmins that are released upon cell damage as DAMPs in cancers and inflammatory diseases. Conclusions In this chapter, we define HSP and MMP as moonlighting proteins and review their roles in inflammatory diseases such as RA. Keywords Alarmin · DAMP · Extracellular HSP · Extracellular vesicle · Intracellular MMP · Moonlighting protein · Rheumatoid arthritis
Abbreviations APC ATP B BBB CCL CRPC DAMP DC ECM EV HA HMGB HSP IL IL-1R L-EV LRP1 MAPK MEV MHC MMP Mφ NALP3 NK NLR NLS NOD OA OSCC P2 PAMP PC-3 PI3K/AKT
antigen-presenting cell adenosine triphosphate B lymphocyte blood-brain barrier C-C motif chemokine ligand castration-resistant prostate cancer damage-associated molecular pattern dendritic cell extracellular matrix extracellular vesicle hyaluronan high-mobility group protein with a ‘Box’ domain heat shock protein interleukin interleukin 1 receptor large extracellular vesicle low-density lipoprotein receptor-related protein 1 microtubule associated protein kinase metastatic oral cancer-derived extracellular vesicle major histocompatibility
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