Abstract
Many aggregate-prone proteins, including proteins with long polyglutamine or polyalanine tracts, cause human diseases. Polyalanine proteins may also be present in the tissue of polyglutamine diseases as a result of frameshifting of the primary polyglutamine-encoding (CAG)n repeat mutation. We have generated a Drosophila model expressing green fluorescent protein tagged to 37 alanines that manifests both toxicity and inclusion formation in various tissues. Surprisingly, we show that this aggregate-prone protein with a polyalanine expansion can also protect against polyglutamine toxicity, which can be explained by induction of heat-shock response. A heat-shock response was also seen in an oculopharyngeal muscular dystrophy mouse model expressing an authentic polyalanine-expanded protein. We also show that long polyalanines can protect against a pro-apoptotic stimulus or the toxicity caused by the long polyalanines themselves. Thus, overexpression of an aggregate-prone protein without any normal functions can result in both pathogenic and protective effects in cell culture and in vivo.
Original language | English |
---|---|
Journal | Human Molecular Genetics |
Volume | 15 |
Issue number | 3 |
Pages (from-to) | 453-465 |
Number of pages | 13 |
ISSN | 0964-6906 |
DOIs | |
Publication status | Published - 01.02.2006 |
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)