apoB and apobec1, two genes key to lipid metabolism, are transcriptionally regulated by p53

Osnat Ashur-Fabian*, Adi Har-Zahav, Aviv Shaish, Hila Wiener Amram, Ofer Margalit, Orly Weizer-Stern, Dan Dominissini, Dror Harats, Ninette Amariglio, Gideon Rechavi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

p53 is an established tumor suppressor gene activating the transcription of multiple target genes. Apolipoprotein B (apo B), a dietary lipid transporter, occurs as apo B-100 and apoB-48, created by a premature stop codon by apo B mRNA-editing enzyme complex 1 (apobec1). We have identified p53 response elements (p53RE) in the genes encoding for apoB and apobec1, cloned these novel p53RE and by performing functionality, chromatin immunoprecipitation (ChIP) and expression assays in cancer cell lines, confirmed that these genes are transcriptionally regulated by p53. In C57bl/6 mice treated with adriamycin, a potent p53 inducer, intestinal/liver mRNA expression of apoB and apobec1 and liver apoB editing levels were elevated. In irradiated wild type C57bl6 mice but not p53 knockout mice, liver and intestine apoB but not apobec1 mRNA expression was elevated. In this work, we have identified that p53 regulates the transcription of two central lipid metabolism players. We further show, for the first time, an involvement of p53 in the RNA editing process, through the transcription of apobec1. Our findings may reveal a previously unknown role for p53 in the direct regulation of atherogenic lipoproteins and a possible role for these genes in classical p53 activities.

Original languageEnglish
Pages (from-to)3785-3794
Number of pages10
JournalCell Cycle
Volume9
Issue number18
DOIs
StatePublished - 15 Sep 2010

Funding

FundersFunder number
Kahn Family Foundation
Flight Attendant Medical Research Institute
Israel Cancer Association
Wolfson Family Charitable Trust

    Keywords

    • Apobec1
    • Cancer
    • Lipids
    • Response-element
    • Transcription
    • apoB
    • p53

    Fingerprint

    Dive into the research topics of 'apoB and apobec1, two genes key to lipid metabolism, are transcriptionally regulated by p53'. Together they form a unique fingerprint.

    Cite this