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PXD027782

PXD027782 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAOH1996, a small molecule ligand of PCNA, modulates PCNA interaction with RPB1
DescriptionTargeting 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.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_06:57:25.854.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBrett Lomenick
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-08-06 03:45:09ID requested
12023-08-02 22:46:26announced
22023-11-14 06:57:26announced2023-11-14: 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 affiliationCaltech Proteome Exploration Laboratory
contact emails.d.garbis@gmail.com
lab head
Brett Lomenick
contact affiliationCaltech Proteome Exploration Lab
contact emaillomenick@caltech.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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