IKKalpha and IKKbeta regulation of DNA damage-induced cleavage of huntingtin.

ABSTRACT:

Background

Proteolysis of huntingtin (Htt) plays a key role in the pathogenesis of Huntington's disease (HD). However, the environmental cues and signaling pathways that regulate Htt proteolysis are poorly understood. One stimulus may be the DNA damage that accumulates in neurons over time, and the subsequent activation of signaling pathways such as those regulated by IkappaB kinase (IKK), which can influence neurodegeneration in HD.

Methodology/principal findings

We asked whether DNA damage induces the proteolysis of Htt and if activation of IKK plays a role. We report that treatment of neurons with the DNA damaging agent etoposide or gamma-irradiation promotes cleavage of wild type (WT) and mutant Htt, generating N-terminal fragments of 80-90 kDa. This event requires IKKbe

SUBMITTER: Khoshnan A 

PROVIDER: S-EPMC2685016 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature