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dc.contributor.authorGupta, S
dc.contributor.authorRead, D E
dc.contributor.authorDeepti, A
dc.contributor.authorCawley, K
dc.contributor.authorGupta, A
dc.contributor.authorOommen, D
dc.contributor.authorVerfaillie, T
dc.contributor.authorMatus, S
dc.contributor.authorSmith, M A
dc.contributor.authorMott, J L
dc.contributor.authorAgostinis, P
dc.contributor.authorHetz, C
dc.contributor.authorSamali, A
dc.date.accessioned2018-09-20T16:09:57Z
dc.date.available2018-09-20T16:09:57Z
dc.date.issued2012-06-01
dc.identifier.citationGupta, S; Read, D E; Deepti, A; Cawley, K; Gupta, A; Oommen, D; Verfaillie, T; Matus, S; Smith, M A; Mott, J L; Agostinis, P; Hetz, C; Samali, A (2012). Perk-dependent repression of mir-106b-25 cluster is required for er stress-induced apoptosis. Cell Death and Disease 3 ,
dc.identifier.issn2041-4889
dc.identifier.urihttp://hdl.handle.net/10379/11772
dc.description.abstractActivation of the unfolded protein response sensor PKR-like endoplasmic reticulum kinase (Perk) attenuates endoplasmic reticulum (ER) stress levels. Conversantly, if the damage is too severe and ER function cannot be restored, this signaling branch triggers apoptosis. Bcl-2 homology 3-only family member Bim is essential for ER stress-induced apoptosis. However, the regulatory mechanisms controlling Bim activation under ER stress conditions are not well understood. Here, we show that downregulation of the miR-106b-25 cluster contributes to ER stress-induced apoptosis and the upregulation of Bim. Hypericin-mediated photo-oxidative ER damage induced Perk-dependent cell death and led to a significant decrease in the levels of miRNAs belonging to miR-106b-25 cluster in wild-type (WT) but not in Perk(- / -) MEFs. Further, we show that expression of miR-106b-25 and Mcm-7 (host gene of miR-106b-25) is co-regulated through the transcription factors Atf4 (activating transcription factor 4) and Nrf2 (nuclear factor-erythroid-2-related factor 2). ER stress increased the activity of WT Bim 3'UTR (untranslated region) construct but not the miR-106b-25 recognition site-mutated Bim 3'UTR construct. Overexpression of miR-106b-25 cluster inhibits ER stress-induced cell death in WT but did not confer any further protection in Bim-knockdown cells. Further, we show downregulation in the levels of miR-106b-25 cluster in the symptomatic SOD1(G86R) transgenic mice. Our results suggest a molecular mechanism whereby repression of miR-106b-25 cluster has an important role in ER stress-mediated increase in Bim and apoptosis. Cell Death and Disease (2012) 3, e333; doi:10.1038/cddis.2012.74; published online 28 June 2012
dc.publisherSpringer Nature
dc.relation.ispartofCell Death and Disease
dc.subjectmir-106b-25
dc.subjectunfolded protein response
dc.subjectapoptosis
dc.subjectbim
dc.subjectatf4
dc.subjectnrf2
dc.subjectunfolded protein response
dc.subjectamyotrophic-lateral-sclerosis
dc.subjectendoplasmic-reticulum stress
dc.subjectoxidative stress
dc.subjecttranscription factor
dc.subjectmessenger-rna
dc.subjectcell-death
dc.subjectexpression
dc.subjectactivation
dc.subjectdisease
dc.titlePerk-dependent repression of mir-106b-25 cluster is required for er stress-induced apoptosis
dc.typeArticle
dc.identifier.doi10.1038/cddis.2012.74
dc.local.publishedsourcehttp://www.nature.com/cddis/journal/v3/n6/pdf/cddis201274a.pdf
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