PXD023983

PXD023983 is an original dataset announced via ProteomeXchange.

Title	Discovery of RSV-induced BRD4 protein interactions using native immunoprecipitation and parallel accumulation – serial fragmentation (PASEF) mass spectrometry
Description	Respiratory Syncytial Virus (RSV) causes severe inflammation and airway pathology in children and the elderly by infecting the epithelial cells of the upper and lower respiratory tract. RSV replication is sensed by intracellular pattern recognition receptors upstream of the IRF and NF-$\upkappa$B transcription factors. These proteins coordinate an innate inflammatory response via Bromodomain containing protein 4 (BRD4), a protein that functions as a scaffold for unknown transcriptional regulators. To better understand the pleiotropic regulatory function of BRD4, we examine the BRD4 interactome and identify how RSV infection dynamically alters it. To accomplish these goals, we leverage native immunoprecipitation and Parallel Accumulation – Serial Fragmentation (PASEF) mass spectrometry to examine BRD4 complexes isolated from human alveolar epithelial cells in the absence or presence of RSV infection. In addition, we explore the role of BRD4's acetyl-lysine binding bromodomains in mediating these interactions by using a highly selective competitive bromodomain inhibitor. We identify 101 proteins that are significantly enriched in the BRD4 complex and are responsive to both RSV-infection and BRD4 inhibition. These proteins are highly enriched in transcription factors and transcriptional coactivators. Among them, we identify members of the AP1 transcription factor complex, a complex important in innate signaling and cell stress responses. We independently confirm the BRD4/AP1 interaction in primary human small airway epithelial cells. We conclude that BRD4 recruits multiple transcription factors during RSV infection in a manner dependent on acetyl-lysine binding domain interactions. This data suggests that BRD4 recruits transcription factors to target its RNA processing complex to regulate gene expression in innate immunity and inflammation.
HostingRepository	PRIDE
AnnounceDate	2021-03-17
AnnouncementXML	Submission_2021-03-17_00:05:22.420.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Morgan Mann
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monoacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-03 23:57:54	ID requested
⏵ 1	2021-03-17 00:05:22	announced

Dataset with its publication pending

submitter keyword: Human, Lung, AP-MS, BRD4, RSV,

Allan Brasier
contact affiliation	Institute for Clinical and Translational Research (ICTR), University of Wisconsin-Madison, Madison, WI, 53705, USA
contact email	abrasier@wisc.edu
lab head
Morgan Mann
contact affiliation	UW-Madison
contact email	mwmann@wisc.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/2021/03/PXD023983

PRIDE project URI

• PRIDE
  1. PXD023983
     1. Label: PRIDE project
     2. Name: Discovery of RSV-induced BRD4 protein interactions using native immunoprecipitation and parallel accumulation – serial fragmentation (PASEF) mass spectrometry