Yonsei Med J.  2018 Jun;59(4):463-469. 10.3349/ymj.2018.59.4.463.

Moonlighting Activity of Secreted Inflammation-Regulatory Proteins

Affiliations
  • 1Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.
  • 2Department of Otolaryngology-Head and Neck Surgery, Center for Thyroid Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
  • 3Laboratory of Signal Transduction, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea. baeksj@snu.ac.kr

Abstract

Moonlighting proteins exhibit multiple activities in different cellular compartments, and their abnormal regulation could play an important role in many diseases. To date, many proteins have been identified with moonlighting activity, and more such proteins are being gradually identified. Among the proteins that possess moonlighting activity, several secreted proteins exhibit multiple activities in different cellular locations, such as the extracellular matrix, nucleus, and cytoplasm. While acute inflammation starts rapidly and generally disappears in a few days, chronic inflammation can last for months or years. This is generally because of the failure to eliminate the cause of inflammation, along with repeated exposure to the inflammatory agent. Chronic inflammation is now considered as an overwhelming burden to the general wellbeing of patients and noted as an underlying cause of several diseases. Moonlighting proteins can contribute to the process of chronic inflammation; therefore, it is imperative to overview some proteins that exhibit multiple functions in inflammatory diseases. In this review, we will focus on inflammation, particularly unravelling several well-known secreted proteins with multiple functions in different cellular locations.

Keyword

Inflammation; moonlighting protein; multiple function; secretion

MeSH Terms

Cytoplasm
Extracellular Matrix
Humans
Inflammation

Figure

  • Fig. 1 Pathways of secreted moonlighting proteins that exhibit anti-inflammatory properties. NAG-1, thymosin β4, and ISG15 are classically known as secreted proteins. However, recent data suggest that these proteins possess biological activity at different translocation sites, such as the nucleus and cytoplasm. Anti-inflammatory activity of ISG15 in the nucleus has been reported; however, the anti-inflammatory activity of NAG-1 and thymosin β4 needs to be elucidated. Details are provided in the text. NAG-1, a nonsteroidal anti-inflammatory drug, activated gene-1; ISG15, interferon-stimulated gene 15; G-actin, globular actin; F-actin, fibrous actin.

  • Fig. 2 Pathways of secreted moonlighting proteins that exhibit pro-inflammatory property. MMP12 and bFGF are classically known as secreted proteins that regulate ECM and cytokine activity, respectively. These proteins also play significant biological roles in the nucleus as a transcriptional regulator and DNA repair modulator, respectively. Details are provided in the text. MMP12, matrix metalloproteinase-12; bFGF, basic fibroblast growth factor; ECM, extracellular matrix; NFKBIA, NFKB inhibitor alpha; PSME3, proteasome activator complex subunit 3; IBD, inflammatory bowel disease; RA, retinoic acid; ICP, intrahepatic cholestasis of pregnancy; SPARCL1, SPARC-like protein 1.


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