IL-1β Promotes a New Function of DNase I as a Transcription Factor for the Fas Receptor Gene

Frontiers in Cell and Developmental Biology
Dhivya ThiyagarajanOle Petter Rekvig

Abstract

Recently we described that endonuclease inactive DNase I translocated into the nucleus in response to increased endogenous IL-1β expression. Here, we demonstrate impact and function of translocated DNase I in tubular cells. Effect of cytokines on expression level and nuclear localisation of DNase I and corresponding levels of Fas receptor (FasR) and IL-1β were determined by confocal microscopy, qPCR and western blot analyses, in presence or absence of siRNA against IL-1β and DNase I mRNA. Nuclear DNase I bound to theFASpromotor region as determined by chromatin immuno-precipitation analysis. Data demonstrate that; (i) translocation of DNase I depended on endogenousde novo-expressed IL-1β, (ii) nuclear DNase I boundFASDNA, (iii) FasR expression increased after translocation of DNase I, (iv) interaction ofexogenousFas ligand (FasL) with upregulated FasR induced apoptosis in human tubular cells stimulated with TNFα. Thus, translocated DNase I most probably binds the promoter region of theFASgene and function as a transcription factor for FasR. In conclusion, DNase I not only executes chromatin degradationduringapoptosis and necrosis, but also primes the cellsforapoptosis by enhancing FasR expression.

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Citations

Jun 6, 2020·Frontiers in Cell and Developmental Biology·Zhiwen FanYong Xu
Aug 24, 2019·Progress in Lipid Research·Tian-Tian ZhangChang-Hu Xue
May 5, 2021·Protein Expression and Purification·Lijuan YuDayong Jin
Jun 1, 2021·Chemico-biological Interactions·Mihajlo GajićAndrija Šmelcerović
Jun 26, 2021·Chemistry & Biodiversity·Mihajlo GajićAndrija Šmelcerović

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Methods Mentioned

BETA
nuclear translocation
confocal microscopy
transfection
PCR
protein
ChIP
ELISA
Assay
nuclear
Confocal

Software Mentioned

ImageJ
Fuji Image J
ProXima C16
Graph pad Prism

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis