PQBP-1/Npw38, a Nuclear Protein Binding to the Polyglutamine Tract, Interacts with U5-15kD/dim1p via the Carboxyl-Terminal Domain

PQBP1, a factor linked to intellectual disability, affects alternative splicing associated with neurite outgrowth

“…Previous work has indicated an association of PQBP1 with mRNA processing factors (Waragai et al 1999(Waragai et al , 2000Okazawa et al 2002;Komuro et al 1999). We discovered that PQBP1 colocalizes with SC35 in nuclear speckles ( Fig.…”

“…Recent studies also reported that PQBP1 was dynamically associated with stress granules and interacted with dynactin components, indicating a possible role for PQBP1 in RNA transport or cytoplasmic RNA processing (Kunde et al 2011). Also, PQBP1 has been implicated in premRNA splicing: PQBP1 interacts with known splicing factors such as WBP11 and U5-15KD (Komuro et al 1999;Waragai et al 2000) and is part of the early spliceosome (Makarova et al 2004). Consistent with this view, a disease-associated mutant of PQBP1 decreased splicing efficiency (Tapia et al 2010).…”

“…WBP11, a previously known PQBP1 interactor (Komuro et al 1999), was detected in all three replicate purifications of wild-type PQBP1, confirming the validity of our approach (Supplemental Table S1). U5-15KD, another proposed interactor of PQBP1 (Waragai et al 2000), was not identified, possibly because of cell specificity or because the interaction is not strong enough to be detected in our tandem affinity purification. DAG showed significantly reduced splicing factor association compared with wild-type PQBP1, while Y65C lost associations with all splicing-related factors (Supplemental Table S1).…”

Y65C Missense Mutation in the WW Domain of the Golabi-Ito-Hall Syndrome Protein PQBP1 Affects Its Binding Activity and Deregulates Pre-mRNA Splicing

“…The PQBP1 (polyglutamine tract-binding protein 1) 2 gene encodes a nuclear protein of 38 kDa that is abundantly expressed in the central nervous system (1)(2)(3)(4)(5). Several studies have provided evidence for a role of the PQBP1 protein in the pathogenesis of polyglutamine expansion diseases, including spinocerebellar ataxia type 1 (6,7).…”

Mutant huntingtin impairs Ku70-mediated DNA repair

“…Various cellular functions, including transcription (Okazawa et al, 2002;Sugars and Rubinsztein, 2003;Butler and Bates, 2006;Ross and Thompson, 2006), splicing (Jackson et al, 1998;Shibata et al, 2000;Waragai et al, 2000), proteasome activity (Johnston et al, 1998;Venkatraman et al, 2004;Bennett et al, 2007), autophagy (Ravikumar et al, 2004;Iwata et al, 2005;Pandey et al, 2007), axonal transport (Gauthier et al, 2004), synaptic transmission (Li et al, 2000(Li et al, , 2004Murphy et al, 2000), endocytosis (Metzler et al, 2001;Singaraja et al, 2002), mitochondrial membrane stability (Panov et al, 2002;Ruan et al, 2004), energy metabolism (Cui et al, 2006;St-Pierre et al, 2006;Weydt et al, 2006), and oxidative stress response (Wyttenbach et al, 2002;Giorgini et al, 2005; for review see Lin and Beal, 2006), are affected in neurons expressing mutant polyQ proteins. Understanding of these pathogenic pathways is definitely necessary for developing therapeutics (Di Prospero and Fischbeck, 2005;Soong and Paulson, 2007).…”