- 积分
- 0
- 威望
- 0
- 包包
- 3465
|
Cells use autophagy for bulk degradation, in what is often thought of as a nonspecific process. That perception, however, might not be accurate, according to data from Bj?rk?y et al. (page 603). Some autophagy substrates are polyubiquitinated and appear to be targeted for destruction.
4 ~7 @* _ b/ u+ O
0 e$ m) \ t& U4 X- u' uProtein aggregates, such as those found in Huntington's disease, contain polyubiquitinated proteins, as well as the polyubiquitin-binding protein p62.
7 ]2 `/ d+ _$ i" h0 }3 }* k; c
, V) d4 y F( ?; d% n/ N* iThe team found that p62 accumulation into protein aggregates depended on its polyubiquitin binding domain and on a polymerization domain, PB1, which allows large chains of p62 to form. p62 also colocalized with LC3, a protein that binds to the autophagosome membrane. Moreover, inhibition of autophagy blocked p62 degradation.
" j* A4 w0 A3 B- R" G7 a y8 m3 Y0 ^! t5 g* f/ j& r4 T7 v! x- M* i1 Z
In cells expressing a mutant huntingtin protein, aggregates containing p62 and LC3 were even more common than in the HeLa cells initially studied. Reducing the amount of p62 expressed caused a higher proportion of the cells in the population to undergo apoptosis.) v E) M$ h8 E
$ d/ T7 k) D& A. O5 G0 s' G+ tThe data suggest that p62 helps identify substrates for autophagy via its polyubiquitin binding domain. Using its PB1 domain p62 forms a shell around the aggregate and somehow facilitates an interaction with LC3, which is likely an early step in targeting to autophagosomes. The work provides a molecular link between recognition of polyubiquitinated protein aggregates and garbage disposal by autophagy, and suggests that cells may use protein aggregation as a protective response.(p62 (green) links to ubiquitinated prote) |
|