scholarly journals Aip regulates cAMP signalling and GH secretion in GH3 cells

2013 ◽  
Vol 20 (4) ◽  
pp. 495-505 ◽  
Author(s):  
R Formosa ◽  
A Xuereb-Anastasi ◽  
J Vassallo
Keyword(s):  
Gh3 Cells ◽  
Luciferase Reporter ◽  
Interacting Protein ◽  
Over Expression ◽  
Knock Down ◽  
Camp Signalling ◽  
Gh Secretion ◽  
Aryl Hydrocarbon ◽  
Reporter Assays ◽  
Aip Gene

Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been linked to predisposition to pituitary adenomas. However, the mechanism by which this occurs remains unknown. AIP interacts with a number of interesting proteins, including members of the cAMP signalling pathway that has been shown to be consistently altered in pituitary tumours. The functional role of Aip was investigated using both over-expression and knock down of Aip in GH3 cells. cAMP signalling and its downstream effectors, including GH secretion, were then investigated. cAMP signalling was analysed using cAMP assays, cAMP-response element-promoter luciferase reporter assays, real-time PCR and finally secreted GH quantification. Over-expression of wild-type (WT)-Aip reduced forskolin-induced cAMP signalling at the total cAMP level, luciferase reporter activity and target gene expression, when compared with empty vector and the non-functional R304X mutant. Additionally, GH secretion was reduced in WT-Aip over-expressing GH3 cells treated with forskolin. Knock down of endogenous Aip resulted in increased cAMP signalling but a decrease in GH secretion was also noted. Inhibition of phosphodiesterase activity using general and selective inhibitors did not completely ablate the effect of Aip on forskolin-augmented cAMP signalling. A mechanism by which Aip acts as a tumour suppressor, by maintaining a low cAMP signalling and concentration, is suggested. Mutations of Aip render the protein incapable of such activity. This effect appears not to be mediated by the AIP–PDE interaction, suggesting the involvement of other interacting partners in mediating this outcome.

scholarly journals Hierarchical Action of Mulberry miR156 in the Vegetative Phase Transition

2021 ◽  
Vol 22 (11) ◽  
pp. 5550
Author(s):  
Hongshun Li ◽  
Yiwei Luo ◽  
Bi Ma ◽  
Jianqiong Hu ◽  
Zhiyuan Lv ◽  
...  
Keyword(s):  
Phase Transition ◽  
Arabidopsis Thaliana ◽  
Woody Plants ◽  
Luciferase Reporter ◽  
Vegetative Phase ◽  
Promoter Sequences ◽  
Over Expression ◽  
Degradome Sequencing ◽  
Pathway Expression ◽  
Reporter Assays

The vegetative phase transition is a prerequisite for flowering in angiosperm plants. Mulberry miR156 has been confirmed to be a crucial factor in the vegetative phase transition in Arabidopsis thaliana. The over-expression of miR156 in transgenic Populus × canadensis dramatically prolongs the juvenile phase. Here, we find that the expression of mno-miR156 decreases with age in all tissues in mulberry, which led us to study the hierarchical action of miR156 in mulberry. Utilizing degradome sequencing and dual-luciferase reporter assays, nine MnSPLs were shown to be directly regulated by miR156. The results of yeast one-hybrid and dual-luciferase reporter assays also revealed that six MnSPLs could recognize the promoter sequences of mno-miR172 and activate its expression. Our results demonstrate that mno-miR156 performs its role by repressing MnSPL/mno-miR172 pathway expression in mulberry. This work uncovered a miR156/SPLs/miR172 regulation pathway in the development of mulberry and fills a gap in our knowledge about the molecular mechanism of vegetative phase transition in perennial woody plants.

scholarly journals Mutation analysis of aryl hydrocarbon receptor interacting protein (AIP) gene in colorectal, breast, and prostate cancers

2007 ◽  
Vol 96 (2) ◽  
pp. 352-356 ◽  
Author(s):  
M Georgitsi ◽  
A Karhu ◽  
R Winqvist ◽  
T Visakorpi ◽  
K Waltering ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Mutation Analysis ◽  
Interacting Protein ◽  
Aryl Hydrocarbon ◽  
Prostate Cancers ◽  
Aip Gene

scholarly journals Transcriptional Regulation of gga-miR-451 by AhR:Arnt in Mycoplasma gallisepticum (HS Strain) Infection

2019 ◽  
Vol 20 (12) ◽  
pp. 3087 ◽  
Author(s):  
Yabo Zhao ◽  
Yali Fu ◽  
Yingfei Sun ◽  
Mengyun Zou ◽  
Xiuli Peng
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Chromatin Immunoprecipitation ◽  
Regulatory Region ◽  
Mycoplasma Gallisepticum ◽  
Luciferase Reporter ◽  
Binding Motif ◽  
Aryl Hydrocarbon ◽  
Transcriptional Regulatory ◽  
Reporter Assays ◽  
Transcriptional Regulatory Region

MicroRNAs (miRNAs) have been determined to be important regulators for pathogenic microorganism infection. However, it is largely unclear how miRNAs are triggered during pathogen infection. We previously reported that the up-regulation of gga-miR-451 negatively regulates the Mycoplasma gallisepticum (MG)-induced production of inflammatory cytokines via targeting tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein zeta (YWHAZ). The aim of this study was to investigate the mechanism regulating gga-miR-451 in MG infection in chickens. Analysis of gga-miR-451 precursor, pri-miR-451, and pre-miR-451 indicated that the regulation occurred transcriptionally. We also identified the transcriptional regulatory region of gga-miR-451 that contained consensus-binding motif for aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (Arnt) complex, which is known as the transcription factor that regulates gene expression. Luciferase reporter assays combined with chromatin immunoprecipitation (ChIP) demonstrated that AhR:Arnt bound directly to the promoter elements of gga-miR-451, which were responsible for gga-miR-451 transcription in the context of MG infection. Furthermore, upregulation of AhR:Arnt significantly induced gga-miR-451 and inhibited YWHAZ expression, suggesting that AhR:Arnt may play an anti-inflammatory role in MG infection. This discovery suggests that induced gga-miR-451 expression is modulated by AhR:Arnt in response to MG infection.

scholarly journals Oncoprotein LAMTOR5 activates GLUT1 via upregulating NF-κB in liver cancer

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 264-270 ◽  
Author(s):  
Jing Zhou ◽  
Yajun Li ◽  
Danhua Li ◽  
Zhi Liu ◽  
Jie Zhang
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Western Blotting ◽  
Glucose Transporter ◽  
Luciferase Reporter ◽  
Pcr Assay ◽  
Glucose Transporter 1 ◽  
Over Expression ◽  
Liver Cancer Cells ◽  
Reporter Assays

AbstractObjectiveAccumulating reports reveal that serving as an oncogenic factor LAMTOR5 is involved in the progression of many specific cancers. Glucose transporter 1 (GLUT1) is frequently identified in many cancers. However, it remains unexplored whether GLUT1 plays a role in LAMTOR5-enhanced liver cancer. Here, we aim to decipher the function of LAMTOR5 in the regulation of GLUT1 in liver cancer.MethodsThe effect of LAMTOR5 on GLUT1 was analyzed using Western blotting and RT-PCR assay. Dose-increased over-expression or silencing of LAMTOR5 was performed through transient transfection. LAMTOR5-activated GLUT1 promoter was revealed by luciferase reporter assay. The regulation of GLUT1 by LAMTOR5/NF-κB was examined via Western blotting and luciferase reporter assays.ResultsThe data showed that in liver cancer cells under the administration with dose-increased LAMTOR5, the level of mRNA and protein of GLUT1 was obviously raised. Our data revealed that the activities of GLUT1 promoter were induced by LAMTOR5. Then, we found that the elevation of GLUT 1 mediated by LAMTOR5 slowed when the inhibitor or siRNAs of NF-κB was introduced into the liver cancer cells. Conclusion. LAMTOR5 is responsible for the activation of GLUT1 via transcription factor NF-κB in liver cancer.

scholarly journals Frequency of AIP Gene Mutations in Young Patients With Acromegaly: A Registry-Based Study

2014 ◽  
Vol 99 (12) ◽  
pp. E2789-E2793 ◽  
Author(s):  
Christof Schöfl ◽  
Jürgen Honegger ◽  
Michael Droste ◽  
Martin Grussendorf ◽  
Reinhard Finke ◽  
...  
Keyword(s):  
Family History ◽  
Direct Sequencing ◽  
Positive Family History ◽  
Young Patients ◽  
Gene Mutations ◽  
Interacting Protein ◽  
Aryl Hydrocarbon ◽  
Number Of Patients ◽  
The Individual ◽  
Aip Gene

Context: Familial and sporadic GH-secreting pituitary adenomas are associated with mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene. Patients with an AIP mutation (AIPmut) tend to have more aggressive tumors occurring at a younger age. Objective: The objective of the study was to investigate the frequency of AIPmut in patients diagnosed at 30 years of age or younger. Design: The German Acromegaly Registry database (1795 patients in 58 centers) was screened for patients diagnosed with acromegaly at 30 years of age or younger (329 patients). Sixteen centers participated and 91 patients consented to AIPmut analysis. Intervention: DNA was analyzed by direct sequencing and multiplex ligation dependent probe amplification Main outcome Measures: The number of patients with AIPmut was measured. Results: Five patients had either a mutation (c.490C>T, c.844C>T, and c.911G>A, three males) or gross deletions of exons 1 and 2 of the AIP gene (n = 2, one female). The overall frequency of an AIPmut was 5.5%, and 2.3% or 2.4% in patients with an apparently sporadic adenoma or macroadenoma, respectively. By contrast, three of four patients (75%) with a positive family history were tested positive for an AIPmut. Except for a positive family history, there were no significant differences between patients with and without an AIPmut. Conclusions: The frequency of AIPmut in this registry-based cohort of young patients with acromegaly is lower than previously reported. Patients with a positive family history should be tested for an AIPmut, whereas young patients without an apparent family history should be screened, depending on the individual cost to benefit ratio.

scholarly journals Aggressive pituitary adenomas occurring in young patients in a large Polynesian kindred with a germline R271W mutation in the AIP gene

2009 ◽  
Vol 161 (5) ◽  
pp. 799-804 ◽  
Author(s):  
Juliet E Jennings ◽  
Marianthi Georgitsi ◽  
Ian Holdaway ◽  
Adrian F Daly ◽  
Maria Tichomirowa ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Index Case ◽  
Young Patients ◽  
Case Series ◽  
Pituitary Tumors ◽  
Maximum Diameter ◽  
Interacting Protein ◽  
Functional Studies ◽  
Aryl Hydrocarbon ◽  
Aip Gene

ObjectiveMutations in the aryl hydrocarbon receptor-interacting protein (AIP) were recently shown to confer a pituitary adenoma predisposition in patients with familial isolated pituitary adenomas (FIPA). We report a large Samoan FIPA kindred from Australia/New Zealand with an R271W mutation that was associated with aggressive pituitary tumors.Design and methodsCase series with germline screening of AIP and haplotype analyses among R271W families.ResultsThis previously unreported kindred consisted of three affected individuals that either presented with or had first symptoms of a pituitary macroadenoma in late childhood or adolescence. The index case, a 15-year-old male with incipient gigantism and his maternal aunt, had somatotropinomas, and the maternal uncle of the index case had a prolactinoma. All tumors were large (15, 40, and 60 mm maximum diameter) and two required transcranial surgery and radiotherapy. All three affected subjects and ten other unaffected relatives were found to be positive for a germline R271W AIP mutation. Comparison of the single nucleotide polymorphism patterns among this family and two previously reported European FIPA families with the same R271W mutation demonstrated no common ancestry.ConclusionsThis kindred exemplifies the aggressive features of pituitary adenomas associated with AIP mutations, while genetic analyses among three R271W FIPA families indicate that R271W represents a mutational hotspot that should be studied further in functional studies.

Aryl hydrocarbon receptor interacting protein(AIP) gene mutation analysis in children and adolescents with sporadic pituitary adenomas

2008 ◽  
Vol 69 (4) ◽  
pp. 621-627 ◽  
Author(s):  
Marianthi Georgitsi ◽  
Ernesto De Menis ◽  
Salvatore Cannavò ◽  
Markus J. Mäkinen ◽  
Karoliina Tuppurainen ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Children And Adolescents ◽  
Gene Mutation ◽  
Mutation Analysis ◽  
Pituitary Adenomas ◽  
Interacting Protein ◽  
Aryl Hydrocarbon ◽  
Aip Gene ◽  
Gene Mutation Analysis
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