dc.contributor.author | Lin, Stephen S. | |
dc.contributor.author | Bassik, Michael C. | |
dc.contributor.author | Suh, Heikyung | |
dc.contributor.author | Nishino, Mari | |
dc.contributor.author | Arroyo, Jason D. | |
dc.contributor.author | Hahn, William C. | |
dc.contributor.author | Korsmeyer, Stanley J. | |
dc.contributor.author | Roberts, Thomas M. | |
dc.date.accessioned | 2019-10-13T16:03:27Z | |
dc.date.issued | 2006 | |
dc.identifier.citation | Lin, 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.issn | 0021-9258 | |
dc.identifier.issn | 1083-351X | |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:41542806 | * |
dc.description.abstract | Anti-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.iso | en_US | |
dc.publisher | American Society for Biochemistry and Molecular Biology | |
dash.license | LAA | |
dc.title | PP2A Regulates BCL-2 Phosphorylation and Proteasome-mediated Degradation at the Endoplasmic Reticulum | |
dc.type | Journal Article | |
dc.description.version | Version of Record | |
dc.relation.journal | The Journal of Biological Chemistry | |
dash.depositing.author | Hahn, William C::31ef101c797e643e0dfa48f8bce1dc3c::600 | |
dc.date.available | 2019-10-13T16:03:27Z | |
dash.workflow.comments | 1Science Serial ID 106410 | |
dc.identifier.doi | 10.1074/jbc.M602648200 | |
dash.source.volume | 281;32 | |
dash.source.page | 23003-23012 | |