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dc.contributor.authorLin, Stephen S.
dc.contributor.authorBassik, Michael C.
dc.contributor.authorSuh, Heikyung
dc.contributor.authorNishino, Mari
dc.contributor.authorArroyo, Jason D.
dc.contributor.authorHahn, William C.
dc.contributor.authorKorsmeyer, Stanley J.
dc.contributor.authorRoberts, Thomas M.
dc.date.accessioned2019-10-13T16:03:27Z
dc.date.issued2006
dc.identifier.citationLin, Stephen S., Michael C. Bassik, Heikyung Suh, Mari Nishino, Jason D. Arroyo, William C. Hahn, Stanley J. Korsmeyer, and Thomas M. Roberts. 2006. “PP2A Regulates BCL-2 Phosphorylation and Proteasome-Mediated Degradation at the Endoplasmic Reticulum.” Journal of Biological Chemistry 281 (32): 23003–12. doi:10.1074/jbc.M602648200.
dc.identifier.issn0021-9258
dc.identifier.issn1083-351X
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41542806*
dc.description.abstractAnti-apoptotic activity of BCL-2 is mediated by phosphorylation at the endoplasmic reticulum (ER), but how this phosphorylation is regulated and the mechanism(s) by which it regulates apoptosis are unknown. We purified macromolecular complexes containing BCL-2 from ER membranes and found that BCL-2 co-purified with the main two subunits of the serine/threonine phosphatase, PP2A. The association of endogenous PP2A and BCL-2 at the ER was verified by co-immunoprecipitation and microcystin affinity purification. Knock down or pharmacological inhibition of PP2A caused degradation of phosphorylated BCL-2 and led to an overall reduction in BCL-2 levels. We found that this degradation was due to the action of the proteasome acting selectively at the ER. Conversely, overexpression of PP2A caused elevation in endogenous BCL-2. Most importantly, we found that PP2A knock down sensitized cells to several classes of death stimuli (including ER stress), but this effect was abolished in a genetic background featuring knock in of a non-phosphorylatable BCL-2 allele. These studies support the hypothesis that PP2A-mediated dephosphorylation of BCL-2 is required to protect BCL-2 from proteasome-dependent degradation, affecting resistance to ER stress.
dc.language.isoen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dash.licenseLAA
dc.titlePP2A Regulates BCL-2 Phosphorylation and Proteasome-mediated Degradation at the Endoplasmic Reticulum
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalThe Journal of Biological Chemistry
dash.depositing.authorHahn, William C::31ef101c797e643e0dfa48f8bce1dc3c::600
dc.date.available2019-10-13T16:03:27Z
dash.workflow.comments1Science Serial ID 106410
dc.identifier.doi10.1074/jbc.M602648200
dash.source.volume281;32
dash.source.page23003-23012


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