title: Transcript stabilization by the RNA-binding protein HuR is regulated by cellular retinoic acid-binding protein 2.
abstract: The RNA-binding protein HuR binds at 3' untranslated regions (UTRs) of target transcripts, thereby protecting them against degradation. We show that HuR directly interacts with cellular retinoic acid-binding protein 2 (CRABP2), a protein known to transport RA from the cytosol to the nuclear retinoic acid receptor (RAR). Association with CRABP2 dramatically increases the affinity of HuR toward target mRNAs and enhances the stability of such transcripts, including that of Apaf-1, the major protein in the apoptosome. We show further that its cooperation with HuR contributes to the ability of CRABP2 to suppress carcinoma cell proliferation. The data show that CRABP2 displays antioncogenic activities both by cooperating with RAR and by stabilizing antiproliferative HuR target transcripts. The observation that CRABP2 controls mRNA stabilization by HuR reveals that in parallel to participating in transcriptional regulation, the protein is closely involved in posttranscriptional regulation of gene expression.
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Vreeland
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Shuiliang
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Liraz
authors.initials: L
authors.lastname: Levi
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Daniella
authors.initials: D
authors.lastname: de Barros Rossetto
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA noa.noy@case.edu.
authors.forename: Noa
authors.initials: N
authors.lastname: Noy
mesh_terms: D000818:Animals; D001059:Apoproteins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D051959:ELAV Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D020871:RNA Stability / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C506593:Apaf1 protein, mouse; D001059:Apoproteins; D053477:Apoptotic Protease-Activating Factor 1; D051959:ELAV Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin