scholarly journals Fra, Fra Away: The complex role of activator protein 1 in liver injury

Hepatology ◽  
2013 ◽  
Vol 59 (1) ◽  
pp. 19-20 ◽  
Author(s):  
David A. Brenner
Keyword(s):  
Liver Injury ◽  
Activator Protein 1 ◽  
Activator Protein

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.

T-5224, a selective inhibitor of c-Fos/activator protein-1, attenuates lipopolysaccharide-induced liver injury in mice

2012 ◽  
Vol 34 (12) ◽  
pp. 2175-2182 ◽  
Author(s):  
Shinichiro Izuta ◽  
Masaaki Ueki ◽  
Masaki Ueno ◽  
Kahoru Nishina ◽  
Shunichi Shiozawa ◽  
...  
Keyword(s):  
Liver Injury ◽  
Selective Inhibitor ◽  
Activator Protein 1 ◽  
Activator Protein

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 Estrogen receptor-α mediates human multidrug resistance associated protein 3 induction by 17α-ethynylestradiol. Role of activator protein-1

2013 ◽  
Vol 86 (3) ◽  
pp. 401-409 ◽  
Author(s):  
María Laura Ruiz ◽  
Juan Pablo Rigalli ◽  
Agostina Arias ◽  
Silvina Stella Maris Villanueva ◽  
Claudia Banchio ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Multidrug Resistance ◽  
Estrogen Receptor Α ◽  
Activator Protein 1 ◽  
Activator Protein
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