This study investigates the role of poly(ADP-ribosyl)ation (PARylation) in regulating the function of the RNA-binding protein HuR during apoptosis. The key findings are:
PARylation of HuR by PARP1/2 under normal conditions promotes its nuclear localization by facilitating its interaction with the nuclear import factor TRN2.
Depletion or inhibition of PARP1/2 leads to decreased PARylation of HuR, resulting in its cytoplasmic accumulation and cleavage by caspases, which enhances its pro-apoptotic function.
HuR contains a conserved PAR-binding motif (HuR-PBS) within its nucleocytoplasmic shuttling domain (HNS). Mutating this motif prevents PAR binding and causes HuR to accumulate in the cytoplasm, where it is cleaved and promotes apoptosis.
The non-covalent binding of PAR to the HuR-PBS regulates its association with the nuclear import factor TRN2, thereby controlling HuR's subcellular localization and pro-apoptotic function.
In summary, the study demonstrates that PARP1/2-mediated PARylation of HuR is a key regulatory mechanism that modulates its localization and pro-apoptotic activity, providing insights into how HuR function is controlled during cell death processes.
toiselle kielelle
lähdeaineistosta
biorxiv.org
Tärkeimmät oivallukset
by Ashour,K., H... klo www.biorxiv.org 08-09-2023
https://www.biorxiv.org/content/10.1101/2023.08.07.552262v1Syvällisempiä Kysymyksiä