PXD027782

PXD027782 is an original dataset announced via ProteomeXchange.

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

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.

Dataset with its publication pending

submitter keyword: APIM motif,PCNA, RPB1, AOH1996, and transcription-replication conflict

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/08/PXD027782

PRIDE project URI

• PRIDE
  1. PXD027782
     1. Label: PRIDE project
     2. Name: AOH1996, a small molecule ligand of PCNA, modulates PCNA interaction with RPB1