DNA or Protein Methylation-Dependent Regulation of Activator Protein-1 Function

Kim, Eunji; Ahuja, Akash; Kim, Mi‐Yeon; Cho, Jae Youl

doi:10.3390/cells10020461

Cited by 17 publications

(17 citation statements)

References 107 publications

(125 reference statements)

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“…Reporter gene assays showed that RuvBL1 overexpression significantly decreased AP-1 luciferase activity in TRAIL-treated cells ( Figure 3A ). AP-1 activity responds to extracellular stimulation mainly via JNK and ERK pathways ( 31 ). However, RuvBL1 overexpression did not affect JNK and ERK activation induced by TRAIL ( Figure 3B ).…”

Section: Resultsmentioning

confidence: 99%

RuvBL1 Maintains Resistance to TRAIL-Induced Apoptosis by Suppressing c-Jun/AP-1 Activity in Non-Small Cell Lung Cancer

Zhou²,

Zhang³

et al. 2021

Front. Oncol.

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Lung cancer is the common malignant tumor with the highest death rate in the world. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a potential anticancer agent induces selective apoptotic death of human cancer cells. Unfortunately, approximately half of lung cancer cell lines are intrinsically resistant to TRAIL-induced cell death. In this study, we identified RuvBL1 as a repressor of c-Jun/AP-1 activity, contributing to TRAIL resistance in lung cancer cells. Knocking down RuvBL1 effectively sensitized resistant cells to TRAIL, and overexpression of RuvBL1 inhibited TRAIL-induced apoptosis. Moreover, there was a negative correlation expression between RuvBL1 and c-Jun in lung adenocarcinoma by Oncomine analyses. High expression of RuvBL1 inversely with low c-Jun in lung cancer was associated with a poor overall prognosis. Taken together, our studies broaden the molecular mechanisms of TRAIL resistance and suggest the application of silencing RuvBL1 synergized with TRAIL to be a novel therapeutic strategy in lung cancer treatment.

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Section: Resultsmentioning

confidence: 99%

RuvBL1 Maintains Resistance to TRAIL-Induced Apoptosis by Suppressing c-Jun/AP-1 Activity in Non-Small Cell Lung Cancer

Zhou²,

Zhang³

et al. 2021

Front. Oncol.

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“…Moreover, disordered regions within TFs, which become structured upon interaction with binding partners (“coupled folding and binding”) may also represent attractive therapeutic targets. Indeed, these regions have a higher proportion of potential cavities and can more easily adjust to small molecules [ 65 , 66 , 67 , 68 , 69 ]. Below we discuss some potential approaches to target AP-1 TFs in MM ( Figure 2 and Table 2 ).…”

Section: Targeting Ap-1 Tfs For MM Therapymentioning

confidence: 99%

“…Epigenetic alterations activate or suppress AP-1 activities and offer the opportunity to selectively target AP-1 transcriptomes [ 68 ].…”

Section: Targeting Ap-1 Tfs For MM Therapymentioning

confidence: 99%

“…In addition, protein arginine methyltransferases (PRMTs) are ‘writers’ of arginine methylation in histone and non-histone proteins and are involved in aberrant epigenetic networks in cancers. The selective PRMT1 inhibitor TC-E 5003 (TC-E) downregulates the nuclear translocation of c-Jun as well as of NFκB subunits p65 and p50, and directly regulates c-Jun gene expression following lipopolysaccharides (LPS) treatment [ 68 , 85 ].…”

Section: Targeting Ap-1 Tfs For MM Therapymentioning

confidence: 99%

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The Role of AP-1 Transcription Factors in Plasma Cell Biology and Multiple Myeloma Pathophysiology

Fan

Podar

2021

Cancers

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Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the clonal expansion of malignant plasma cells within the bone marrow. Activator Protein-1 (AP-1) transcription factors (TFs), comprised of the JUN, FOS, ATF and MAF multigene families, are implicated in a plethora of physiologic processes and tumorigenesis including plasma cell differentiation and MM pathogenesis. Depending on the genetic background, the tumor stage, and cues of the tumor microenvironment, specific dimeric AP-1 complexes are formed. For example, AP-1 complexes containing Fra-1, Fra-2 and B-ATF play central roles in the transcriptional control of B cell development and plasma cell differentiation, while dysregulation of AP-1 family members c-Maf, c-Jun, and JunB is associated with MM cell proliferation, survival, drug resistance, bone marrow angiogenesis, and bone disease. The present review article summarizes our up-to-date knowledge on the role of AP-1 family members in plasma cell differentiation and MM pathophysiology. Moreover, it discusses novel, rationally derived approaches to therapeutically target AP-1 TFs, including protein-protein and protein-DNA binding inhibitors, epigenetic modifiers and natural products.

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“…Among them, the AP-1 pathway is regulated by the transcription factor AP-1, which is responsible for regulating cell differentiation, cell cycle progression, and apoptosis. The AP-1 pathway consists of c-Fos and c-Jun families, and its transcriptional activation is mediated through the dimerization of these two subunits [ 17 , 18 , 19 , 20 , 21 ]. Originally located in the cytosol, c-Fos and c-Jun translocate into the nucleus and dimerize after they are activated by their upstream kinases, mitogen-activated protein kinases (MAPKs).…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Activities of an Anti-Histamine Drug, Loratadine, by Suppressing TAK1 in AP-1 Pathway

Jang

Hunto

Kim

et al. 2022

IJMS

Self Cite

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Loratadine is an anti-histamine routinely used for treating allergies. However, recent findings have shown that Loratadine may also have anti-inflammatory functions, while their exact mechanisms have not yet been fully uncovered. In this paper, we investigated whether Loratadine can be utilized as an anti-inflammatory drug through a series of in vitro and in vivo experiments using a murine macrophage cell line and an acute gastritis mouse model. Loratadine was found to dramatically reduce the expression of pro-inflammatory genes, including MMP1, MMP3, and MMP9, and inhibit AP-1 transcriptional activation, as demonstrated by the luciferase assay. Therefore, we decided to further explore its role in the AP-1 signaling pathway. The expression of c-Jun and c-Fos, AP-1 subunits, was repressed by Loratadine and, correspondingly, the expression of p-JNK, p-MKK7, and p-TAK1 was also inhibited. In addition, Loratadine was able to reduce gastric bleeding in acute gastritis-induced mice; Western blotting using the stomach samples showed reduced p-c-Fos protein levels. Loratadine was shown to effectively suppress inflammation by specifically targeting TAK1 and suppressing consequent AP-1 signaling pathway activation and inflammatory cytokine production.

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DNA or Protein Methylation-Dependent Regulation of Activator Protein-1 Function

Cited by 17 publications

References 107 publications

RuvBL1 Maintains Resistance to TRAIL-Induced Apoptosis by Suppressing c-Jun/AP-1 Activity in Non-Small Cell Lung Cancer

RuvBL1 Maintains Resistance to TRAIL-Induced Apoptosis by Suppressing c-Jun/AP-1 Activity in Non-Small Cell Lung Cancer

The Role of AP-1 Transcription Factors in Plasma Cell Biology and Multiple Myeloma Pathophysiology

Anti-Inflammatory Activities of an Anti-Histamine Drug, Loratadine, by Suppressing TAK1 in AP-1 Pathway

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