The extracellular role of DNA damage repair protein APE1 in regulation of IL-6 expression
The human apurinic/apyrimidinic endonuclease 1 (APE1) is a pleiotropic nuclear protein with roles in DNA base excision repair pathway as well as in regulation of transcription. Recently, the presence of extracellular plasma APE1 was reported in endotoxemic rats. However, the biological significance...
Saved in:
Published in | Cellular signalling Vol. 39; pp. 18 - 31 |
---|---|
Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier Inc
01.11.2017
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | The human apurinic/apyrimidinic endonuclease 1 (APE1) is a pleiotropic nuclear protein with roles in DNA base excision repair pathway as well as in regulation of transcription. Recently, the presence of extracellular plasma APE1 was reported in endotoxemic rats. However, the biological significance and the extracellular function of APE1 remain unclear. In this study, we found that monocytes secrete APE1 upon inflammatory challenges. Challenging the monocytic cells with extracellular APE1 resulted in the increased expression and secretion of the pro-inflammatory cytokine IL-6. Additionally, the extracellular APE1 treatment activated the transcription factor NF-κB, followed by its increased occupancy at the IL-6 promoter, resulting in the induction of IL-6 expression. APE1-induced IL-6 further served to elicit autocrine and paracrine cellular responses. Moreover, the extracellular IL-6 promoted the secretion of APE1, thus indicating a functional feedforward loop in this pathway. Furthermore, we show that APE1 is secreted through extracellular vesicles formation via endosomal sorting complex required for transport (ESCRT)-dependent pathway. Together, our study demonstrates a novel role of extracellular APE1 in IL-6-dependent cellular responses.
•DNA damage repair protein APE1 is secreted from monocytes upon inflammatory challenges.•Extracellular APE1 induces IL-6 gene expression.•APE1 is secreted through extracellular vesicles formation. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Dr. Somsubhra Nath, Molecular Biology Research and Diagnostic Laboratory, Saroj Gupta Cancer Center and Research Institute, Kolkata, India |
ISSN: | 0898-6568 1873-3913 |
DOI: | 10.1016/j.cellsig.2017.07.019 |