SIRT2 deacetylase regulates the activity of GSK3 isoforms independent of inhibitory phosphorylation.
Elife
; 72018 03 05.
Article
in En
| MEDLINE
| ID: mdl-29504933
ABSTRACT
Glycogen synthase kinase 3 (GSK3) is a critical regulator of diverse cellular functions involved in the maintenance of structure and function. Enzymatic activity of GSK3 is inhibited by N-terminal serine phosphorylation. However, alternate post-translational mechanism(s) responsible for GSK3 inactivation are not characterized. Here, we report that GSK3α and GSK3ß are acetylated at Lys246 and Lys183, respectively. Molecular modeling and/or molecular dynamics simulations indicate that acetylation of GSK3 isoforms would hinder both the adenosine binding and prevent stable interactions of the negatively charged phosphates. We found that SIRT2 deacetylates GSK3ß, and thus enhances its binding to ATP. Interestingly, the reduced activity of GSK3ß is associated with lysine acetylation, but not with phosphorylation at Ser9 in hearts of SIRT2-deficient mice. Moreover, GSK3 is required for the anti-hypertrophic function of SIRT2 in cardiomyocytes. Overall, our study identified lysine acetylation as a novel post-translational modification regulating GSK3 activity.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Processing, Post-Translational
/
Protein Isoforms
/
Glycogen Synthase Kinase 3
/
Sirtuin 2
Limits:
Animals
/
Humans
Language:
En
Journal:
Elife
Year:
2018
Document type:
Article
Affiliation country:
India