TY - JOUR
T1 - Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose
AU - Kloet, Max S.
AU - Chatrin, Chatrin
AU - Mukhopadhyay, Rishov
AU - van Tol, Bianca D.M.
AU - Smith, Rebecca
AU - Rotman, Sarah A.
AU - Tjokrodirijo, Rayman T.N.
AU - Zhu, Kang
AU - Gorelik, Andrii
AU - Maginn, Lucy
AU - Elliott, Paul R.
AU - van Veelen, Peter A.
AU - Ahel, Dragana
AU - Ahel, Ivan
AU - van der Heden van Noort, Gerbrand J.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - Crosstalk between the post-translational modification processes of ubiquitination and ADP-ribosylation occurs in DNA-damage- and immune-responses, in addition the physical linkage of ADP-ribose and ubiquitin is found during bacterial infection. Here, we study the ubiquitination of ADP-ribose mediated by human Deltex E3 ligases and the subsequent fate of the formed hybrid post-translational modification. We prepare a non-hydrolysable ADPr-Ub probe that we employ in a proteomics approach and identify RNF114 as an interacting protein. Using biophysical and biochemical experiments, we validate that RNF114 preferentially interacts with ubiquitinated ADP-ribose over non-modified ubiquitin. Subsequently, RNF114 can elongate the ubiquitinated ADP-ribose with a K11-linked ubiquitin chain. Using domain deletion analysis, we pinpoint the tandem zinc fingers and ubiquitin interacting motif (ZnF2 + ZnF3+UIM) domains of RNF114 to be crucial for recognising ubiquitinated ADP-ribose. Moreover, these domains are essential for the recruitment of RNF114 to the sites of laser-induced DNA damage.
AB - Crosstalk between the post-translational modification processes of ubiquitination and ADP-ribosylation occurs in DNA-damage- and immune-responses, in addition the physical linkage of ADP-ribose and ubiquitin is found during bacterial infection. Here, we study the ubiquitination of ADP-ribose mediated by human Deltex E3 ligases and the subsequent fate of the formed hybrid post-translational modification. We prepare a non-hydrolysable ADPr-Ub probe that we employ in a proteomics approach and identify RNF114 as an interacting protein. Using biophysical and biochemical experiments, we validate that RNF114 preferentially interacts with ubiquitinated ADP-ribose over non-modified ubiquitin. Subsequently, RNF114 can elongate the ubiquitinated ADP-ribose with a K11-linked ubiquitin chain. Using domain deletion analysis, we pinpoint the tandem zinc fingers and ubiquitin interacting motif (ZnF2 + ZnF3+UIM) domains of RNF114 to be crucial for recognising ubiquitinated ADP-ribose. Moreover, these domains are essential for the recruitment of RNF114 to the sites of laser-induced DNA damage.
UR - https://www.scopus.com/pages/publications/105010524728
U2 - 10.1038/s41467-025-61111-7
DO - 10.1038/s41467-025-61111-7
M3 - 文章
C2 - 40634336
AN - SCOPUS:105010524728
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6319
ER -