Cyclic-AMP-dependent protein kinase A regulates apoptosis by stabilizing the BH3-only protein Bim

Author(s): Moujalled, D; Weston, R; Anderton, H; Ninnis, R; Goel, P; Coley, A; Huang, DCS; Wu, L; Strasser, A; Puthalakath, H;
Details: Publication Year 2011-01,Volume 12,Issue #1,Page 77-83
Journal Title: EMBO REPORTS
Publication Type: Journal Article
Abstract: The proapoptotic Bcl2 homology domain 3(BH3)-only protein Bim is controlled by stringent post-translational regulation, predominantly through alterations in phosphorylation status. To identify new kinases involved in its regulation, we carried out a yeast two-hybrid screen using a non-spliceable variant of the predominant isoform-Bim(EL)-as the bait and identified the regulatory subunit of cyclic-AMP-dependent protein kinase A-PRKAR1A-as an interacting partner. We also show that protein kinase A (PKA) is a Bim(EL) isoform-specific kinase that promotes its stabilization. Inhibition of PKA or mutation of the PKA phosphorylation site within Bim(EL) resulted in its accelerated proteasome-dependent degradation. These results might have implications for human diseases that are characterized by abnormally increased PKA activity, such as the Carney complex and dilated cardiomyopathy.
Publisher: NATURE PUBLISHING GROUP
Keywords: PHOSPHORYLATION; ACTIVATION; EXPRESSION; CELLS; DEGRADATION; INHIBITION; RESISTANCE; LYMPHOMA; PRKAR1A; PATHWAY
Publisher's Version: https://doi.org/10.1038/embor.2010.190
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2011-01-01 12:00:00