title: Involvement of ubiquilin-1 transcript variants in protein degradation and accumulation.
abstract: Controlled management of protein levels and quality is essential for normal cellular function. Specific molecular chaperones and foldases monitor the levels and assist correct folding of proteins. The ubiquitin-proteasome system recognizes and degrades misfolded proteins that can otherwise be harmful to cells. However, when misfolded or aggregated proteins excessively accumulate, they may be sequestered to the microtubule-organizing center to form aggresomes. These may then be removed from cells by autophagocytosis. Abnormal protein accumulation and aggregation is a common hallmark of many neurodegenerative diseases. In a recent study, we provide evidence that specific transcript variants (TVs) of ubiquilin-1, which are genetically and functionally associated to Alzheimer's disease (AD), regulate proteasomal and aggresomal targeting of presenilin-1 (PS1), a key player in AD pathogenesis. Our study together with current data provide interesting implications for ubiquilin-1 and its TVs in the pathogenesis of AD and other neurodegenerative diseases involving abnormal protein aggregation.
authors.affiliation: Institute of Clinical Medicine - Neurology; University of Eastern Finland; Kuopio, Finland.
authors.forename: Annakaisa
authors.initials: A
authors.lastname: Haapasalo
authors.forename: Jayashree
authors.initials: J
authors.lastname: Viswanathan
authors.forename: Kaisa Ma
authors.initials: KM
authors.lastname: Kurkinen
authors.forename: Lars
authors.initials: L
authors.lastname: Bertram
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Nico P
authors.initials: NP
authors.lastname: Dantuma
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: Mikko
authors.initials: M
authors.lastname: Hiltunen