RRC ID |
59446
|
著者 |
Bailly AP, Perrin A, Serrano-Macia M, Maghames C, Leidecker O, Trauchessec H, Martinez-Chantar ML, Gartner A, Xirodimas DP.
|
タイトル |
The Balance between Mono- and NEDD8-Chains Controlled by NEDP1 upon DNA Damage Is a Regulatory Module of the HSP70 ATPase Activity.
|
ジャーナル |
Cell Rep
|
Abstract |
Ubiquitin and ubiquitin-like chains are finely balanced by conjugating and de-conjugating enzymes. Alterations in this balance trigger the response to stress conditions and are often observed in pathologies. How such changes are detected is not well understood. We identify the HSP70 chaperone as a sensor of changes in the balance between mono- and poly-NEDDylation. Upon DNA damage, the induction of the de-NEDDylating enzyme NEDP1 restricts the formation of NEDD8 chains, mainly through lysines K11/K48. This promotes APAF1 oligomerization and apoptosis induction, a step that requires the HSP70 ATPase activity. HSP70 binds to NEDD8, and, in vitro, the conversion of NEDD8 chains into mono-NEDD8 stimulates HSP70 ATPase activity. This effect is independent of NEDD8 conjugation onto substrates. The study indicates that the NEDD8 cycle is a regulatory module of HSP70 function. These findings may be important in tumorigenesis, as we find decreased NEDP1 levels in hepatocellular carcinoma with concomitant accumulation of NEDD8 conjugates.
|
巻・号 |
29(1)
|
ページ |
212-224.e8
|
公開日 |
2019-10-1
|
DOI |
10.1016/j.celrep.2019.08.070
|
PII |
S2211-1247(19)31125-8
|
PMID |
31577950
|
PMC |
PMC6899524
|
MeSH |
Adenosine Triphosphatases / genetics*
Amino Acid Sequence
Animals
Carcinogenesis / genetics
Cell Line, Tumor
DNA Damage / genetics*
Endopeptidases / genetics*
Female
HSP70 Heat-Shock Proteins / genetics*
Humans
Lysine / genetics
MCF-7 Cells
Mice
NEDD8 Protein / genetics*
Ubiquitin / genetics
|
IF |
7.815
|
引用数 |
3
|
リソース情報 |
線虫 |
tm1579
tm5454
tm1287 |