RT Journal Article
SR Electronic
T1 A ubiquitination-mediated degradation system to target phospho-14-3-3-binding-motif embedded proteins
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.22.517526
DO 10.1101/2022.11.22.517526
A1 Zhaokai Li
A1 Xiaoqiang Huang
A1 Mohan Li
A1 Ziad Sabry
A1 Y. Eugene Chen
A1 Zhong Wang
A1 Liu Liu
YR 2022
UL http://biorxiv.org/content/early/2022/11/23/2022.11.22.517526.abstract
AB The phosphorylation of 14-3-3 binding motif is involved in many cellular processes. A strategy that enables targeted degradation of phospho-14-3-3-binding-motif embedded (P-14-3-3-BME) proteins for studying their functions is highly desirable for basic research. Here, we report a phosphorylation-induced, ubiquitin-proteasome-system-mediated targeted protein degradation (TPD) strategy that allows specific degradation of P-14-3-3-BME proteins. Specifically, by ligating a modified von Hippel-Lindau E3-ligase with an engineered 14-3-3 bait, we generated a protein chimera referred to as Targeted Degradation of P-14-3-3-BME Protein (TDPP). TDPP can serve as a universal degrader for P-14-3-3-BME proteins based on the specific recognition of the phosphorylation in 14-3-3 binding motifs. TDPP shows high efficiency and specificity to a difopein-EGFP reporter, general and specific P-14-3-3-BME proteins. TDPP can also be applied for the validation of P-14-3-3-BME proteins. These results strongly support TDPP as a powerful tool for 14-3-3 related research.Competing Interest StatementThe authors have declared no competing interest.