PXD027782 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | AOH1996, a small molecule ligand of PCNA, modulates PCNA interaction with RPB1 |
Description | Targeting transcription replication conflicts, a major source of endogenous DNA double stranded breaks and genomic instability, could have important therapeutic implications. When transcription and DNA replication machineries encounter each other on chromosomes, one way to resolve the conflict is temporarily dislodging RNA polymerase II from the conflict sites to enable the replication fork to proceed. Proliferating cell nuclear antigen (PCNA), an essential component of replisomes, plays a critical role in this process. We discovered a small molecule ligand (AOH1996) of PCNA, which targets a binding pocket adjacent to the outer surface region of PCNA known to interact with PIP box and APIM motif proteins. Orally administrable, AOH1996 suppresses tumor growth but causes no discernable side effects. In addition, we found that AOH1996 treatment can stabilize interaction between PCNA and RPB1, the largest subunit of RNA polymerase II. To determine whether the effect of AOH1996 is mediated through affecting PCNA interaction with RPB1, we mutated Y418 within the APIM motif of RPB1 to an alanine in the SK-N-AS cell line by CRISPR and compared changes in protein expression profiles caused by AOH1996 in the parent and mutant SK-N-AS cells. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_06:57:25.854.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Brett Lomenick |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Eclipse |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-08-06 03:45:09 | ID requested | |
1 | 2023-08-02 22:46:26 | announced | |
⏵ 2 | 2023-11-14 06:57:26 | announced | 2023-11-14: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: APIM motif,PCNA, RPB1, AOH1996, and transcription-replication conflict |
Contact List
Spiros D Garbis |
contact affiliation | Caltech Proteome Exploration Laboratory |
contact email | s.d.garbis@gmail.com |
lab head | |
Brett Lomenick |
contact affiliation | Caltech Proteome Exploration Lab |
contact email | lomenick@caltech.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD027782
- Label: PRIDE project
- Name: AOH1996, a small molecule ligand of PCNA, modulates PCNA interaction with RPB1