Back to Search
Start Over
AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity
- Source :
- The FASEB journal (2019)., info:cnr-pdr/source/autori:Alberto Bavelloni # 1, Enrico Focaccia # 1 2, Manuela Piazzi # 1 2, Mirco Raffini 1, Valeriana Cesarini 3, Sara Tomaselli 3, Arianna Orsini 4, Stefano Ratti 4, Irene Faenza 4, Lucio Cocco 4, Angela Gallo 3, William L Blalock 1 2/titolo:AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and-2 inhibits deaminase activity./doi:/rivista:The FASEB journal/anno:2019/pagina_da:/pagina_a:/intervallo_pagine:/volume
- Publication Year :
- 2019
- Publisher :
- Federation of American Societies for Experimental Biology, [Bethesda, Md.] , Stati Uniti d'America, 2019.
-
Abstract
- Murine thymoma viral oncogene homolog (AKT) kinases target both cytosolic and nuclear substrates for phosphorylation. Whereas the cytosolic substrates are known to be closely associated with the regulation of apoptosis and autophagy or metabolism and protein synthesis, the nuclear substrates are, for the most part, poorly understood. To better define the role of nuclear AKT, potential AKT substrates were isolated from the nuclear lysates of leukemic cell lines using a phosphorylated AKT substrate antibody and identified in tandem mass spectrometry. Among the proteins identified was adenosine deaminase acting on RNA (ADAR)1p110, the predominant nuclear isoform of the adenosine deaminase acting on double-stranded RNA. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively, and overexpression of the phosphomimic mutants ADAR1p110 (T738D) and ADAR2 (T553D) resulted in a 50-100% reduction in editase activity. Thus, activation of AKT has a direct and major impact on RNA editing.-Bavelloni, A., Focaccia, E., Piazzi, M., Raffini, M., Cesarini, V., Tomaselli, S., Orsini, A., Ratti, S., Faenza, I., Cocco, L., Gallo, A., Blalock, W. L. AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity.
- Subjects :
- nucleu
Adenosine Deaminase
kinase
Models, Biological
Biochemistry
Substrate Specificity
protein-protein interaction
Adenosine deaminase
Cell Line, Tumor
RNA EDITING
Genetics
medicine
Protein biosynthesis
ADAR2
Humans
Phosphorylation
Molecular Biology
Protein kinase B
Cell Nucleus
Binding Sites
biology
Chemistry
Kinase
AKT
RNA-Binding Proteins
RNA
Adenosine
Recombinant Proteins
Cell biology
Enzyme Activation
HEK293 Cells
Amino Acid Substitution
oncology
ADAR
Mutagenesis, Site-Directed
biology.protein
Proto-Oncogene Proteins c-akt
Biotechnology
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- The FASEB journal (2019)., info:cnr-pdr/source/autori:Alberto Bavelloni # 1, Enrico Focaccia # 1 2, Manuela Piazzi # 1 2, Mirco Raffini 1, Valeriana Cesarini 3, Sara Tomaselli 3, Arianna Orsini 4, Stefano Ratti 4, Irene Faenza 4, Lucio Cocco 4, Angela Gallo 3, William L Blalock 1 2/titolo:AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and-2 inhibits deaminase activity./doi:/rivista:The FASEB journal/anno:2019/pagina_da:/pagina_a:/intervallo_pagine:/volume
- Accession number :
- edsair.doi.dedup.....9f46eb30ccfc2917bfd44a04b3576065