The Balance between Mono- and NEDD8-Chains Controlled by NEDP1 upon DNA Damage Is a Regulatory Module of the HSP70 ATPase Activity
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.
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BibTeX
@article{bailly2026balance,
title = {{The Balance between Mono- and NEDD8-Chains Controlled by NEDP1 upon DNA Damage Is a Regulatory Module of the HSP70 ATPase Activity}},
author = {Aymeric Bailly and Aurelien Perrin and Marina Serrano-Macia and Chantal Maghames and Orsolya Leidecker and Helene Trauchessec and M.L. Martinez-Chantar and Anton Gartner and Dimitris Xirodimas},
journal = {Cell Reports},
year = {2026},
month = sep,
doi = {10.1016/j.celrep.2019.08.070},
url = {https://hal.science/hal-05751775v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - The Balance between Mono- and NEDD8-Chains Controlled by NEDP1 upon DNA Damage Is a Regulatory Module of the HSP70 ATPase Activity
AU - Aymeric Bailly
AU - Aurelien Perrin
AU - Marina Serrano-Macia
AU - Chantal Maghames
AU - Orsolya Leidecker
AU - Helene Trauchessec
AU - M.L. Martinez-Chantar
AU - Anton Gartner
AU - Dimitris Xirodimas
PY - 2026
DA - 2026/09/16
JO - Cell Reports
DO - 10.1016/j.celrep.2019.08.070
UR - https://hal.science/hal-05751775v1
AB - 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.
SN - 2211-1247
SN - 2211-1247
ER -