The Ubiquitin-Proteasome System in Huntington’s Disease: Are Proteasomes Impaired, Initiators of Disease, or Coming to the Rescue?

Figure 3

Potential proteasomal pathways for polyQ degradation. (1). Hybrid-proteasomes can recognize ubiquitinated proteins by the 19S cap and release the polyQ peptides faster due to an open gate conformation facilitated by PA28. (2) 26S proteasomes may be able to degrade mhtt but not the actual polyQ tracts. The released polyQ peptide could be targeted by PA28-capped proteasomes. (3) Changing the catalytic activity by immuno-subunit replacement might improve degradation preference for polyQ sequences.