Hide metadata

dc.date.accessioned2020-05-28T18:28:45Z
dc.date.available2020-05-28T18:28:45Z
dc.date.created2018-10-25T15:23:02Z
dc.date.issued2018
dc.identifier.citationSkah, Seham Richartz, Nina Duthil, Eva Gilljam, Karin Margaretha Bindesbøll, Christian Naderi, Elin Hallan Eriksen, Agnete Bratsberg Ruud, Ellen Dirdal, Marta Maria Simonsen, Anne Blomhoff, Heidi Kiil . cAMP-mediated autophagy inhibits DNA damage-induced death of leukemia cells independent of p53. OncoTarget. 2018, 9(54), 30434-30449
dc.identifier.urihttp://hdl.handle.net/10852/76384
dc.description.abstractAutophagy is important in regulating the balance between cell death and survival, with the tumor suppressor p53 as one of the key components in this interplay. We have previously utilized an in vitro model of the most common form of childhood cancer, B cell precursor acute lymphoblastic leukemia (BCP-ALL), to show that activation of the cAMP signaling pathway inhibits p53-mediated apoptosis in response to DNA damage in both cell lines and primary leukemic cells. The present study reveals that cAMP-mediated survival of BCP-ALL cells exposed to DNA damaging agents, involves a critical and p53-independent enhancement of autophagy. Although autophagy generally is regarded as a survival mechanism, DNA damage-induced apoptosis has been linked both to enhanced and reduced levels of autophagy. Here we show that exposure of BCP-ALL cells to irradiation or cytotoxic drugs triggers autophagy and cell death in a p53-dependent manner. Stimulation of the cAMP signaling pathway further augments autophagy and inhibits the DNA damage-induced cell death concomitant with reduced nuclear levels of p53. Knocking-down the levels of p53 reduced the irradiation-induced autophagy and cell death, but had no effect on the cAMP-mediated autophagy. Moreover, prevention of autophagy by bafilomycin A1 or by the ULK-inhibitor MRT68921, diminished the protecting effect of cAMP signaling on DNA damage-induced cell death. Having previously proposed a role of the cAMP signaling pathway in development and treatment of BCP-ALLs, we here suggest that inhibitors of autophagy may improve current DNA damage-based therapy of BCP-ALL - independent of p53.
dc.languageEN
dc.publisherImpact Journals LLC
dc.rightsAttribution 3.0 Unported
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/
dc.titlecAMP-mediated autophagy inhibits DNA damage-induced death of leukemia cells independent of p53
dc.typeJournal article
dc.creator.authorSkah, Seham
dc.creator.authorRichartz, Nina
dc.creator.authorDuthil, Eva
dc.creator.authorGilljam, Karin Margaretha
dc.creator.authorBindesbøll, Christian
dc.creator.authorNaderi, Elin Hallan
dc.creator.authorEriksen, Agnete Bratsberg
dc.creator.authorRuud, Ellen
dc.creator.authorDirdal, Marta Maria
dc.creator.authorSimonsen, Anne
dc.creator.authorBlomhoff, Heidi Kiil
cristin.unitcode185,51,0,0
cristin.unitnameInstitutt for medisinske basalfag
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode0
dc.identifier.cristin1623614
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=OncoTarget&rft.volume=9&rft.spage=30434&rft.date=2018
dc.identifier.jtitleOncoTarget
dc.identifier.volume9
dc.identifier.issue54
dc.identifier.startpage30434
dc.identifier.endpage30449
dc.identifier.doihttps://doi.org/10.18632/oncotarget.25758
dc.identifier.urnURN:NBN:no-79476
dc.type.documentTidsskriftartikkel
dc.type.peerreviewedPeer reviewed
dc.source.issn1949-2553
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/76384/3/Skah%2Bet%2Bal%252C%2B2018.pdf
dc.type.versionPublishedVersion
dc.relation.projectNFR/262652


Files in this item

Appears in the following Collection

Hide metadata

Attribution 3.0 Unported
This item's license is: Attribution 3.0 Unported