Title

Acetylation: a new key to unlock tau's role in neurodegeneration.

Journal

Alzheimer's research & therapy

Volume

6

Issue

None

Pages

29

Date

2014-01-01

Authors

Carlomagno Y | Cook C | Petrucelli L | Stankowski JN | Stetler C

We demonstrate that elevated HDAC6 activity increases phosphorylation of tau at the 12E8 epitope (pS262/356), a phospho-epitope present within the KXGS motifs of tau’s microtubule-binding domain. The phosphorylation of KXGS motifs within tau by the kinase Par-1/MARK2 is required for tau proteotoxicity in Drosophila [29], observed at very early stages of NFT formation in AD brain [30], and appears to prime tau for subsequent phosphorylation events

In particular, previous studies have demonstrated that the tau ubiquitin ligase, CHIP, is unable to bind and ubiquitinate tau species phosphorylated by Par-1/MARK2 on the 12E8 epitope (S262/356) [33], a p-tau species that is also resistant to degradation upon treatment with Hsp90 inhibitors [32,33]. Tau phosphorylated at the PHF1 epitope (S396/404) is still susceptible to degradation following Hsp90 inhibition and actually exhibits an enhanced interaction with Hsp90

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.