Ontology highlight
ABSTRACT:
SUBMITTER: Uchida T
PROVIDER: S-EPMC4707540 | biostudies-literature | 2016 Jan
REPOSITORIES: biostudies-literature
Uchida Tsukasa T Tamaki Yoshitaka Y Ayaki Takashi T Shodai Akemi A Kaji Seiji S Morimura Toshifumi T Banno Yoshinori Y Nishitsuji Kazuchika K Sakashita Naomi N Maki Takakuni T Yamashita Hirofumi H Ito Hidefumi H Takahashi Ryosuke R Urushitani Makoto M
Scientific reports 20160111
The molecular machinery responsible for cytosolic accumulation of misfolded TDP-43 in amyotrophic lateral sclerosis (ALS) remains elusive. Here we identified a cullin-2 (CUL2) RING complex as a novel ubiquitin ligase for fragmented forms of TDP-43. The von Hippel Lindau protein (VHL), a substrate binding component of the complex, preferentially recognized misfolded TDP-43 at Glu246 in RNA-recognition motif 2. Recombinant full-length TDP-43 was structurally fragile and readily cleaved, suggesting ...[more]