Parkin interacts with the proteasome subunit alpha 4

• Published in: FEBS letters 2006-07, Vol.579 (18), p.3913-3919
• Main Authors: Dachsel, J C, Lucking, C B, Deeg, S, Schultz, E, Lalowski, M, Casademunt, E, Corti, O, Hampe, C, Patenge, N, Vaupel, K, Yamamoto, A, Dichgans, M, Brice, A, Wanker, E E, Kahle, P J, Gasser, T
• Format: Article
• Language: English
• ISSN: 0014-5793
• DOI: 10.1016/j.febslet.2005.06.003

Mutations in the parkin gene encoding an E3 ligase are responsible for autosomal recessive Parkinson's disease. Putative parkin substrates and interacting partners have been identified, but the molecular mechanism underlying parkin-related neurodegeneration is still unclear. We have identified the 20S proteasomal subunit alpha 4 (synonyms: PSMA7, XAPC7, subunit alpha type 7) as a new interacting partner of parkin. The C-terminal IBR-RING domain of parkin and the C-terminal part of alpha 4 were essential for the interaction. Biochemical studies revealed that alpha 4 was not a substrate for parkin-dependent ubiquitylation. Putative functions of the interaction might therefore be substrate presentation to the proteasome or regulation of proteasomal activity. Full-length parkin and parkin lacking the N-terminal ubiquitin-like domain slightly increased the proteasomal activity in HEK 293T cells, in line with the latter hypothesis.