Proteomics

Dataset Information

0

Piperlongumine (PL) conjugates induce targeted protein degradation


ABSTRACT: PROteolysis Targeting Chimeras (PROTACs) are bifunctional molecules that degrade target proteins through recruiting E3 ligases. However, their application is limited in part because few E3 ligases can be recruited by known E3 ligase ligands. In this study, we identified piperlongumine (PL), a natural product, as a covalent E3 ligase recruiter, which induces CDK9 degradation when it is conjugated with SNS-032, a CDK9 inhibitor. To evaluate the specificity of the PL-SNS-032 lead conjugate named 955, TMT-based proteomics were conducted to compare 955 with its warhead SNS-032 in MOLT4 cells. As expected, cells exhibited a significant reduction of CDK9 after treatment with 0.1 µM 955 for 1 h and 6 h while treatment with 1 µM SNS-032 for 6 h had no significant effect on CDK9. Interestingly, 955, but not SNS-032, can also potently degrade CDK10.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

DISEASE(S): Acute Leukemia

SUBMITTER: Dongwen Lyu  

LAB HEAD: Dongwen Lv

PROVIDER: PXD039385 | Pride | 2024-05-24

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Lyu_030121_Results.xlsx Xlsx
Lyu_030121_SF01.raw Raw
Lyu_030121_SF02.raw Raw
Lyu_030121_SF03.raw Raw
Lyu_030121_SF04.raw Raw
Items per page:
1 - 5 of 22
altmetric image

Publications


Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that degrade target proteins through recruiting E3 ligases. However, their application is limited in part because few E3 ligases can be recruited by known E3 ligase ligands. In this study, we identified piperlongumine (PL), a natural product, as a covalent E3 ligase recruiter, which induces CDK9 degradation when it is conjugated with SNS-032, a CDK9 inhibitor. The lead conjugate 955 can potently degrade CDK9 in a ubiquitin-prote  ...[more]

Similar Datasets

2022-06-26 | GSE206612 | GEO
2024-05-24 | PXD039401 | Pride
2017-09-01 | GSE89385 | GEO
2017-09-01 | GSE89384 | GEO
2011-07-01 | E-GEOD-25452 | biostudies-arrayexpress
2021-02-12 | GSE162205 | GEO
2024-03-12 | PXD049976 | Pride
2011-07-01 | GSE25452 | GEO
2011-02-23 | GSE27449 | GEO
| PRJNA742677 | ENA