TY - JOUR
T1 - OGG1 as an Epigenetic Reader Affects NFκB
T2 - What This Means for Cancer
AU - Vlahopoulos, Spiros
AU - Pan, Lang
AU - Varisli, Lokman
AU - Dancik, Garrett M.
AU - Karantanos, Theodoros
AU - Boldogh, Istvan
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2024/1
Y1 - 2024/1
N2 - 8-oxoguanine glycosylase 1 (OGG1), which was initially identified as the enzyme that catalyzes the first step in the DNA base excision repair pathway, is now also recognized as a modulator of gene expression. What is important for cancer is that OGG1 acts as a modulator of NFκB-driven gene expression. Specifically, oxidant stress in the cell transiently halts enzymatic activity of substrate-bound OGG1. The stalled OGG1 facilitates DNA binding of transactivators, such as NFκB to their cognate sites, enabling the expression of cytokines and chemokines, with ensuing recruitment of inflammatory cells. Recently, we highlighted chief aspects of OGG1 involvement in regulation of gene expression, which hold significance in lung cancer development. However, OGG1 has also been implicated in the molecular underpinning of acute myeloid leukemia. This review analyzes and discusses how these cells adapt through redox-modulated intricate connections, via interaction of OGG1 with NFκB, which provides malignant cells with alternative molecular pathways to transform their microenvironment, enabling adjustment, promoting cell proliferation, metastasis, and evading killing by therapeutic agents.
AB - 8-oxoguanine glycosylase 1 (OGG1), which was initially identified as the enzyme that catalyzes the first step in the DNA base excision repair pathway, is now also recognized as a modulator of gene expression. What is important for cancer is that OGG1 acts as a modulator of NFκB-driven gene expression. Specifically, oxidant stress in the cell transiently halts enzymatic activity of substrate-bound OGG1. The stalled OGG1 facilitates DNA binding of transactivators, such as NFκB to their cognate sites, enabling the expression of cytokines and chemokines, with ensuing recruitment of inflammatory cells. Recently, we highlighted chief aspects of OGG1 involvement in regulation of gene expression, which hold significance in lung cancer development. However, OGG1 has also been implicated in the molecular underpinning of acute myeloid leukemia. This review analyzes and discusses how these cells adapt through redox-modulated intricate connections, via interaction of OGG1 with NFκB, which provides malignant cells with alternative molecular pathways to transform their microenvironment, enabling adjustment, promoting cell proliferation, metastasis, and evading killing by therapeutic agents.
KW - acute myeloid leukemia
KW - cancer stem cells
KW - EMT
KW - gene regulation
KW - innate immunity
KW - lung cancer
KW - microenvironment
KW - NFκB
KW - OGG1
KW - oxidant stress
UR - http://www.scopus.com/inward/record.url?scp=85182186613&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85182186613&partnerID=8YFLogxK
U2 - 10.3390/cancers16010148
DO - 10.3390/cancers16010148
M3 - Review article
C2 - 38201575
AN - SCOPUS:85182186613
SN - 2072-6694
VL - 16
JO - Cancers
JF - Cancers
IS - 1
M1 - 148
ER -