The invention relates to methods and compositions for regulation of GSK3 activity. The invention provides phosphorylated GSK3 polypeptides and antibodies that recognize such polypeptides The invention further includes methods for treating disorders that are associated with elevated or reduced GSK3 activity.

The invention in one aspect relates to recombinant replication competent adenovirus that can replicate in and lyse a host cell comprising in the genome of the adenovirus a coding sequence for a glycogen synthase kinase-3 (GSK3) protein operably linked to an expression control sequence. It also relates, among others, to means and methods for treatment of cancer with a coding sequence for a glycogen synthase kinase-3 (GSK3) protein operably linked to an expression control sequence, preferably in the context of an adenovirus. This work was funded in part by European Union Horizon 2020 research and innovation programme, Marie-Sklodowska-Curie grant number 643130.

Use of glycogen synthase kinase-3 (GSK3) as a protease, and a GSK3-based proteolysis-targeting chimera (PROTAC) and a preparation method and use thereof are provided, belonging to the technical field of proteolysis. The GSK3 and an N-terminal domain, an intermediate domain, or a C-terminal domain thereof have a protease activity and can achieve efficient proteolysis. Based on the GSK3 and other similar proteases, PROTACs can be developed to achieve efficient targeted proteolysis of a target protein.