Identification of differentially expressed three novel transcript variants of mouse <scp>ARNT</scp> gene

Ishqi, Hassan Mubarak; Rehman, Sufia; Sarwar, Tarique; Husain, Mohammed Amir; Tabish, Mohammad

doi:10.1002/iub.1464

Cited by 8 publications

(3 citation statements)

References 59 publications

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“…1, 4, 11 Among them, three HIF- α subunits (HIF-1 α , HIF-2 α , HIF-3 α ) and two beta subunits have been described. 4 The alpha subunits are regulated in an oxygen-dependent manner but differ in their expression pattern and tumourigenic potential.…”

mentioning

confidence: 99%

A HIF-1α-driven feed-forward loop augments HIF signalling in Hep3B cells by upregulation of ARNT

Mandl

Mk²,

Depping

2016

Cell Death Dis

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Oxygen-deprived (hypoxic) areas are commonly found within neoplasms caused by excessive cell proliferation. The transcription factor Aryl hydrocarbon receptor nuclear translocator (ARNT) is part of the hypoxia-inducible factor (HIF) pathway, which mediates adaptive responses to ensure cellular survival under hypoxic conditions. HIF signalling leads to metabolic alterations, invasion/metastasis and the induction of angiogenesis in addition to radio-chemoresistance of tumour cells. Activation of the HIF pathway is based on the abundance of HIF-α subunits, which are regulated in an oxygen-dependent manner and form transcriptional active complexes with ARNT or ARNT2 (also referred as HIF-1β and HIF-2β, respectively). ARNT is considered to be unaffected by hypoxia but certain cell lines, including Hep3B cells, are capable to elevate this transcription factor in response to oxygen deprivation, which implies an advantage. Therefore, the aim of this study was to elucidate the mechanism of hypoxia-dependent ARNT upregulation and to determine implications on HIF signalling. Gene silencing and overexpression techniques were used to alter the expression pattern of HIF transcription factors under normoxic and hypoxic conditions. qRT-PCR and western blotting were performed to measure gene and protein expression, respectively. HIF activity was determined by reporter gene assays. The results revealed a HIF-1α-dependent mechanism leading to ARNT upregulation in hypoxia. Forced expression of ARNT increased reporter activity under normoxic and hypoxic conditions. In conclusion, these findings indicate a novel feed-forward loop and suggest that ARNT might be a limiting factor. Augmented HIF signalling in terms of elevated target gene expression might be advantageous for tumour cells.

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mentioning

confidence: 99%

A HIF-1α-driven feed-forward loop augments HIF signalling in Hep3B cells by upregulation of ARNT

Mandl

Mk²,

Depping

2016

Cell Death Dis

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“…Identification of alternatively spliced variants was performed using a series of bioinformatics tools available online. This method involves excessive use of databases and gene/exon finding tools as discussed earlier . In brief, genomic and transcript sequence of mouse Nur77 gene was obtained from MGI website.…”

Section: Methodsmentioning

confidence: 99%

“…We have followed a methodology that involves computational as well as molecular biology techniques. The approach we follow is simple and time saving in nature and can be successfully used to study alternative splicing of an individual gene . First, with the help of different bioinformatics tools, we predicted existence of novel exons that could participate in alternative splicing with the known exons of Nur77.…”

Section: Introductionmentioning

confidence: 99%

Identification of two novel isoforms of mouse NUR77 lacking N‐terminal domains

et al. 2017

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Nur77 is a member of nuclear receptor superfamily that acts as a transcription factor and regulates expression of multiple genes. Subcellular localization of Nur77 protein plays an important role in the survival and cell death. In this study, we have predicted and confirmed alternatively spliced two new transcripts of Nur77 gene in mouse. The newly identified transcripts have their alternatively spliced first exon located upstream of published 5'-UTR of the gene. Transcription factor binding sites in the possible promoter regions of these transcripts were also analyzed. Expression of novel transcript variants was found to be significantly lower than the already published transcript. New transcript variants encode for NUR77 protein isoforms which are significantly smaller in size due to lack of transactivation domain and a part of DNA binding domain. Western blot analysis using NUR77 specific antibody confirmed the existence of these smaller variants in mouse. Localization of these new isoforms was predicted to be majorly outside the nucleus. In silico analysis of the conceptually translated proteins was performed using different bioinformatics tools. The results obtained in this study offer further insight into novel area of research on extensively studied Nur77. © 2017 IUBMB Life, 69(2):106-114, 2017.

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Identification and expression of alternatively spliced novel isoforms of cancer associated MYD88 lacking death domain in mouse

et al. 2018

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MYD88 is an adaptor protein known to involve in activation of NF-κB through IL-1 receptor and TLR stimulation. It consists of N-terminal death domain and C-terminal Toll/IL-R homology domain that mediates its interaction with IL-1R associated kinase and IL-1R/TLR, respectively. MYD88 contributes to various types of carcinogenesis due to its involvement in oncogene induced inflammation. In the present study, we have recognized two new alternatively spliced variants of MyD88 gene in mouse using bioinformatics tools and molecular biology techniques in combination. The newly identified non-coding exon (NE-1) from 5' upstream region alternatively splices with either exon E-2 or exon E-5 to produce two novel transcript variants MyD88N1 and MyD88N2 respectively. The transcript variant MyD88N1 was expressed in several tissues studied while the variant MyD88N2 was found to be expressed only in the brain. The analysis of the upstream region of novel exon by in silico approach revealed new promoter region PN, which possess potential signature sequences for diverse transcription factors, suggesting complex gene regulation. Studies of post translational modifications of conceptualized amino acid sequences of these isoforms revealed diversity in properties. Western blot analysis further confirmed the expression of protein isoform MYD88N1.

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Identification of differentially expressed three novel transcript variants of mouse ARNT gene

Cited by 8 publications

References 59 publications

A HIF-1α-driven feed-forward loop augments HIF signalling in Hep3B cells by upregulation of ARNT

A HIF-1α-driven feed-forward loop augments HIF signalling in Hep3B cells by upregulation of ARNT

Identification of two novel isoforms of mouse NUR77 lacking N‐terminal domains

Identification and expression of alternatively spliced novel isoforms of cancer associated MYD88 lacking death domain in mouse

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