A review on protein–protein interaction network of APE1/Ref‐1 and its associated biological functions

Abstract

Apurinic/apyrimidinic endonuclease 1 (APE1) is a classic example of functionally variable protein. Besides its well-known role in (i) DNA repair of oxidative base damage, APE1 also plays a critical role in (ii) redox regulation of transcription factors controlling gene expression for cell survival pathways, for which it is also known as redox effector factor 1 (Ref-1), and recent evidences advocates for (iii) coordinated control of other non-canonical protein-protein interaction(s) responsible for significant biological functions in mammalian cells. The diverse functions of APE1 can be ascribed to its ability to interact with different protein partners, owing to the attainment of unfolded domains during evolution. Association of dysregulation of APE1 with various human pathologies, such as cancer, cardiovascular diseases and neurodegeneration, is attributable to its multifunctional nature, and this makes APE1 a potential therapeutic target. This review covers the important aspects of APE1 in terms of its significant protein-protein interaction(s), and this knowledge is required to understand the onset and development of human pathologies and to design or improve the strategies to target such interactions for treatment and management of various human diseases.

Analysis of STAT3 post-translational modifications (PTMs) in human prostate cancer with different Gleason Score

“…Several reports suggested that PDIA3/ERp57 is associated with tumor progression and the modulation of STAT3 activity [60, 61]. Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) is a multifunctional protein that, in addition to its base excision DNA repair activity, exerts a redox control on cancer-associated transcription factors, including STAT3 [62]. Our studies, carried out on sixty-five FFPE tissues, confirmed the constitutively activation of STAT3 protein (pY 705 -STAT3) in tumor samples, without any relevant variation in expression levels between the Gleason grades.…”

Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

“…Furthermore, oxidative stress DNA damage is known to induce APE1 for DNA repair thorough the BER pathway (Thakur et al 2015). APE1 itself favors as a redox co-activator of transcription factors the production of IL-6 Table 4 Univariate and multivariate logistic regression analysis of immunohistochemical expression differences in studied proteins between controls and cases after 34-week gestation…”

“…In this paper, we also focus our attention on the immunohistochemical expression of APE1/ Ref-1 (APE1). This is involved both in the base excision repair (BER) pathway of DNA lesions, acting as the major apurinic/apyrimidinic (AP) endonuclease, and in transcriptional regulation of gene expression, where it functions as a redox co-activator of different transcription factors that could lead to increased interleukin (IL)-6 and IL-8 expression (Cesaratto et al 2013;Thakur et al 2015;Tell et al 2005). IL-6 and IL-8 are two important immune-modulatory cytokines that are part of the senescence-associated secretory phenotype (SASP) (Coppé et al 2008).…”

Paradoxical induction of growth arrest and apoptosis by EGF via the up-regulation of PTEN by activating Redox factor-1/Egr-1 in human lung cancer cells

“…Redox factor-1 (Ref-1) is a multifunctional protein that contributes to both DNA repair and transcriptional regulation [21–23]. Notably, Ref-1 is highly expressed in cancer cells and can have post-translational modifications, protein-protein interactions, redox activity, and roles in DNA repair, suggesting that it could be a useful therapeutic target gene [21–23].…”

“…Notably, Ref-1 is highly expressed in cancer cells and can have post-translational modifications, protein-protein interactions, redox activity, and roles in DNA repair, suggesting that it could be a useful therapeutic target gene [21–23]. Ref-1 increases gene expression by directly associating with transcription factors, including AP-1, EGR1, NF-κB, p53, STAT3, and HIF1α.…”