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

First Author  Moujalled D Year  2011
Journal  EMBO Rep Volume  12
Issue  1 Pages  77-83
PubMed ID  21151042 Mgi Jnum  J:200504
Mgi Id  MGI:5508733 Doi  10.1038/embor.2010.190
Citation  Moujalled D, et al. (2011) Cyclic-AMP-dependent protein kinase A regulates apoptosis by stabilizing the BH3-only protein Bim. EMBO Rep 12(1):77-83
abstractText  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.
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