HUNTINGTIN-ASSOCIATED PROTEIN; HAP1
Several neurodegenerative disorders are known to involve trinucleotide
expansions of the CAG codon for glutamine, including Huntington disease
, spinocerebellar
ataxia type 1 ,
Machado-Joseph disease ,
and spinobulbar muscular atrophy .
Li et al. (1995) identified a cDNA for a
rat brain protein that binds to the mutant HD protein by using the
latter as bait in a 2-hybrid yeast screening assay.
The protein, which they designated HAP1 (huntingtin-associated protein-1),
was found to bind to huntingtin in proportion to the number of glutamines
present in the glutamine repeat region.
Two HAP1 cDNAs were found that differ at the C-terminus, probably
as a result of alternative splicing.
The predicted 599- and 629-amino acid proteins are highly hydrophilic,
rich in charged amino acids, and have no homology to known proteins.
A human cDNA with 96% amino acid identity to the rat protein was also
obtained.
Northern blots showed a 4.0-kb HAP1 transcript in rat brains and RT-PCR
demonstrated expression in human brain, especially in the caudate
and cortex, regions affected in Huntington disease.
Co-immunoprecipitation experiments with rat brain tissue and HAP1-transfected
cells confirmed that HAP1 binds to huntingtin in vivo, though they
had not yet clearly shown the same in human brain tissue.
Li et al. (1995) speculated that HAP1's
ability to bind to glutamine repeats in huntingtin is influenced by
adjacent amino acids, since in their yeast 2-hybrid assays there was
no binding of HAP1 to atrophin-1 (ataxin), even though their atrophin-1
construct contained essentially the same number of glutamine repeats
(21) as did their huntingtin construct (23).
-
1. Li, X.-J.; Li, S.-H.; Sharp, A. H.; Nucifora, F. C., Jr.; Schilling,
G.; Lanahan, A.; Worley, P.; Snyder, S. H.; Ross, C. A. :
- A
huntingtin-associated protein enriched in brain with implications
for pathology. Nature 378: 398-402, 1995.
PubMed ID : 7477378
Alan F. Scott : 11/16/1995
terry : 3/26/1996
joanna : 3/12/1996
mark : 2/5/1996