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

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 461
Author(s):  
Eunji Kim ◽  
Akash Ahuja ◽  
Mi-Yeon Kim ◽  
Jae Youl Cho
Keyword(s):  
Protein Methylation ◽  
Epigenetic Mechanisms ◽  
Activator Protein 1 ◽  
Cellular Processes ◽  
Activator Protein ◽  
Anti Cancer ◽  
Anti Inflammatory ◽  
Cell Signaling Networks ◽  
Cancer Immunotherapies

Epigenetic regulation and modification govern the transcriptional mechanisms that promote disease initiation and progression, but can also control the oncogenic processes, cell signaling networks, immunogenicity, and immune cells involved in anti-inflammatory and anti-tumor responses. The study of epigenetic mechanisms could have important implications for the development of potential anti-inflammatory treatments and anti-cancer immunotherapies. In this review, we have described the key role of epigenetic progression: DNA methylation, histone methylation or modification, and protein methylation, with an emphasis on the activator protein-1 (AP-1) signaling pathway. Transcription factor AP-1 regulates multiple genes and is involved in diverse cellular processes, including survival, differentiation, apoptosis, and development. Here, the AP-1 regulatory mechanism by DNA, histone, or protein methylation was also reviewed. Various methyltransferases activate or suppress AP-1 activities in diverse ways. We summarize the current studies on epigenetic alterations, which regulate AP-1 signaling during inflammation, cancer, and autoimmune diseases, and discuss the epigenetic mechanisms involved in the regulation of AP-1 signaling.

scholarly journals Assessment of the Role of Activator Protein-1 on Transcription of the Mouse Steroidogenic Acute Regulatory Protein Gene

2004 ◽  
Vol 18 (3) ◽  
pp. 558-573 ◽  
Author(s):  
Pulak R. Manna ◽  
Darrell W. Eubank ◽  
Douglas M. Stocco
Keyword(s):  
Binding Site ◽  
Gene Transcription ◽  
Dna Sequences ◽  
Regulatory Protein ◽  
Activator Protein 1 ◽  
Transcriptional Responses ◽  
Activator Protein ◽  
Steroidogenic Acute Regulatory ◽  
Star Gene

Abstract cAMP-dependent mechanisms regulate the steroidogenic acute regulatory (StAR) protein even though its promoter lacks a consensus cAMP response-element (CRE, TGACGTCA). Transcriptional regulation of the StAR gene has been demonstrated to involve combinations of DNA sequences that provide recognition motifs for sequence-specific transcription factors. We recently identified and characterized three canonical 5′-CRE half-sites within the cAMP-responsive region (−151/−1 bp) of the mouse StAR gene. Among these CRE elements, the CRE2 half-site is analogous (TGACTGA) to an activator protein-1 (AP-1) sequence [TGA(C/G)TCA]; therefore, the role of the AP-1 transcription factor was explored in StAR gene transcription. Mutation in the AP-1 element demonstrated an approximately 50% decrease in StAR reporter activity. Using EMSA, oligonucleotide probes containing an AP-1 binding site were found to specifically bind to nuclear proteins obtained from mouse MA-10 Leydig and Y-1 adrenocortical tumor cells. The integrity of the sequence-specific AP-1 element in StAR gene transcription was assessed using the AP-1 family members, Fos (c-Fos, Fra-1, Fra-2, and Fos B) and Jun (c-Jun, Jun B, and Jun D), which demonstrated the involvement of Fos and Jun in StAR gene transcription to varying degrees. Disruption of the AP-1 binding site reversed the transcriptional responses seen with Fos and Jun. EMSA studies utilizing antibodies specific to Fos and Jun demonstrated the involvement of several AP-1 family proteins. Functional assessment of Fos and Jun was further demonstrated by transfecting antisense c-Fos, Fra-1, and dominant negative forms of Fos (A-Fos) and c-Jun (TAM-67) into MA-10 cells, which significantly (P < 0.01) repressed transcription of the StAR gene. Mutation of the AP-1 site in combination with mutations in other cis-elements resulted in a further decrease of StAR promoter activity, demonstrating a functional cooperation between these factors. Mammalian two-hybrid assays revealed high-affinity protein-protein interactions between c-Fos and c-Jun with steroidogenic factor 1, GATA-4, and CCAAT/enhancer binding protein-β. These findings demonstrate that Fos and Jun can bind to the TGACTGA element in the StAR promoter and provide novel insights into the mechanisms regulating StAR gene transcription.

scholarly journals Potential role of acetylsalicilic acid and other non-steroidal anti-inflammatory drugs in cancer risk reduction (literature review)

2021 ◽  
Vol 23 (3) ◽  
Author(s):  
V. V. Buheruk ◽  
O. B. Voloshyna ◽  
L. I. Kovalchuk ◽  
I. V. Balashova ◽  
O. V. Naidionova
Keyword(s):  
Cancer Risk ◽  
Acetylsalicylic Acid ◽  
Potential Role ◽  
Task Force ◽  
Current Systematic Review ◽  
Anti Cancer ◽  
Cancer Types ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

The aim of this review is to analyze and summarize the existing evidence regarding the possibilities of using acetylsalicylic acid (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) to reduce cancer risk. Conclusions. Chronic inflammation facilitates the onset and progress of tumour growth. Anti-cancer properties of acetylsalicylic acid and other non-steroidal anti-inflammatory drugs are mediated via cyclooxygenase COX-dependent mechanisms, as well as other tumorigenic pathways. Current systematic review addresses potential role of ASA and other NSAIDs in reduction of cancer risk for the following localizations: head and neck, lungs, gastrointestinal tract, breast, ovaries, prostate, and skin. The role of ASA in primary prevention of colorectal cancer in specific populations is presented in 2016 U. S. Preventive Services Task Force guidelines. Studies indicate heterogeneous protective potential of ASA against different cancer types, depending on studied population, duration of intake and dose. Influence of non-aspirin NSAIDs on cancer morbidity and mortality is more controversial.

scholarly journals A New Class of Repression Modules Is Critical for Heme Regulation of the Yeast Transcriptional Activator Hap1

1999 ◽  
Vol 19 (6) ◽  
pp. 4324-4333 ◽  
Author(s):  
Angela Hach ◽  
Thomas Hon ◽  
Li Zhang
Keyword(s):  
Biochemical Analysis ◽  
Activator Protein 1 ◽  
Heme Binding ◽  
Systematic Analysis ◽  
High Molecular Weight Complex ◽  
Cellular Processes ◽  
New Class ◽  
Heme Domain ◽  
Heme Regulation

ABSTRACTHeme plays key regulatory roles in numerous molecular and cellular processes for systems that sense or use oxygen. In the yeastSaccharomyces cerevisiae, oxygen sensing and heme signaling are mediated by heme activator protein 1 (Hap1). Hap1 contains seven heme-responsive motifs (HRMs): six are clustered in the heme domain, and a seventh is near the activation domain. To determine the functional role of HRMs and to define which parts of Hap1 mediate heme regulation, we carried out a systematic analysis of Hap1 mutants with various regions deleted or mutated. Strikingly, the data show that HRM1 to -6, located in the previously designated Hap1 heme domain, have little impact on heme regulation. All seven HRMs are dispensable for Hap1 repression in the absence of heme, but HRM7 is required for Hap1 activation by heme. More importantly, we show that a novel class of repression modules—RPM1, encompassing residues 245 to 278; RPM2, encompassing residues 1061 to 1185; and RPM3, encompassing residues 203 to 244—is critical for Hap1 repression in the absence of heme. Biochemical analysis indicates that RPMs mediate Hap1 repression, at least partly, by the formation of a previously identified higher-order complex termed the high-molecular-weight complex (HMC), while HRMs mediate heme activation by permitting heme binding and the disassembly of the HMC. These findings provide significant new insights into the molecular interactions critical for Hap1 repression in the absence of heme and Hap1 activation by heme.

scholarly journals The Potentiation Role of Hepatopoietin on Activator Protein-1 Is Dependent on Its Sulfhydryl Oxidase Activity

2003 ◽  
Vol 278 (49) ◽  
pp. 49022-49030 ◽  
Author(s):  
Xiaoxiao Chen ◽  
Yong Li ◽  
Kaihua Wei ◽  
Li Li ◽  
Wanli Liu ◽  
...  
Keyword(s):  
Oxidase Activity ◽  
Activator Protein 1 ◽  
Sulfhydryl Oxidase ◽  
Activator Protein

Protective role of silibinin on matrix metalloproteinase-2 and activator protein-1 on LoVo cells

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15136-e15136
Author(s):  
C. Lin ◽  
Y. Chen
Keyword(s):  
Colon Cancer ◽  
Matrix Metalloproteinase ◽  
Molecular Mechanisms ◽  
Binding Activity ◽  
Matrix Metalloproteinase 2 ◽  
Lovo Cell ◽  
Activator Protein 1 ◽  
Activator Protein ◽  
Lovo Cells

e15136 Background: Silibinin, a flavonoid and the major active component of milk thistle, has been as a safe diet supplement for several decades. It has been proved with anti-hepatotoxic properties and pleiotropic anticancer capabilities. Current study aimed to investigate the role of silibinin as potential therapeutic target of colon cancer through antiangiogenesis and its related molecular mechanisms with matrix metalloproteinase- 2 (MMP-2) and activator protein-1 (AP-1). Colon cancer cell line, LoVo cells, treated with a major prognostic factor, interleukin-6 (IL-6), was studied. Methods and Results: By western blot analysis, silibinin suppressed MMP- 2 protein expression in time- and concentration-dependent manners. Furthermore, the inhibitors of JNK/AP-1 binding activity abolished the expression of MMP-2 in IL-6-stimulated LoVo cells, but not PI3K pathways. We also demonstrated that silibinin inhibited IL-6- stimulated LoVo cell migration and further tumor angiogenesis, which similar to the effects from addition with AP-1 inhibitor. By EMSA, the binding activity of AP-1 in LoVo cells was also decreased with silibinin treatment. In addition, the imaging of confocal microscopy revealed that AP-1 presentation was attenuated on IL-6-stimulated LoVo cells plus silibinin treatment. Conclusions: Taken together, these data indicated that silibinin inhibits angiogenesis through the suppression of MMP-2 expression and AP-1 binding activity in colon cancer cells. It suggests a novel anti-metastatic application of silibinin in colon cancer chemoprevention. No significant financial relationships to disclose.

scholarly journals ERK: A Double-Edged Sword in Cancer. ERK-Dependent Apoptosis as a Potential Therapeutic Strategy for Cancer

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2509
Author(s):  
Reiko Sugiura ◽  
Ryosuke Satoh ◽  
Teruaki Takasaki
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Tumor Cell Death ◽  
Cancer Treatments ◽  
Erk Activation ◽  
Cellular Processes ◽  
Dual Specificity ◽  
Anti Cancer ◽  
Dual Specificity Phosphatases

The RAF/MEK/ERK signaling pathway regulates diverse cellular processes as exemplified by cell proliferation, differentiation, motility, and survival. Activation of ERK1/2 generally promotes cell proliferation, and its deregulated activity is a hallmark of many cancers. Therefore, components and regulators of the ERK pathway are considered potential therapeutic targets for cancer, and inhibitors of this pathway, including some MEK and BRAF inhibitors, are already being used in the clinic. Notably, ERK1/2 kinases also have pro-apoptotic functions under certain conditions and enhanced ERK1/2 signaling can cause tumor cell death. Although the repertoire of the compounds which mediate ERK activation and apoptosis is expanding, and various anti-cancer compounds induce ERK activation while exerting their anti-proliferative effects, the mechanisms underlying ERK1/2-mediated cell death are still vague. Recent studies highlight the importance of dual-specificity phosphatases (DUSPs) in determining the pro- versus anti-apoptotic function of ERK in cancer. In this review, we will summarize the recent major findings in understanding the role of ERK in apoptosis, focusing on the major compounds mediating ERK-dependent apoptosis. Studies that further define the molecular targets of these compounds relevant to cell death will be essential to harnessing these compounds for developing effective cancer treatments.

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