Cyclic-AMP-dependent protein kinase A regulates apoptosis by stabilizing the BH3-only protein Bim
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
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2011-01-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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