PXD016193

PXD016193 is an original dataset announced via ProteomeXchange.

Title	Antibody RING-Mediated Destruction (ARMeD) of endogenous proteins
Description	To help understand the cellular function of a gene the encoding DNA or mRNA transcript can be manipulated and the consequences observed. However, these approaches do not have a direct effect on the protein product of the gene, which is either permanently abrogated or depleted at a rate defined by the half-life of the protein. Therefore, complete gene deletions and RNA interference of proteins with a very long half-life risk obscuring the direct consequences via compensatory or secondary cellular responses. We therefore sought to develop a single-component system that could induce the rapid degradation of the specific endogenous protein itself. A genetically introduced inducible construct of the RING domain of the ubiquitin E3 ligase RNF4 with a protein-specific camelid nanobody mediates destruction of the target by the ubiquitin proteasome system, a process we describe as Antibody RING-Mediated Destruction (ARMeD). The technique is acutely specific as we observed no off-target protein destruction. Furthermore, bacterially produced nanobody-RING fusion proteins electroporated into cells induce degradation of target within minutes. With the increasing availability of protein-specific nanobodies this method will allow the rapid and specific degradation of a wide range of endogenous proteins.
HostingRepository	PanoramaPublic
AnnounceDate	2020-05-28
AnnouncementXML	Submission_2020-05-28_20:20:10.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	David Dickerson
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Carbamidomethyl; Oxidation
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-07 10:05:32	ID requested
⏵ 1	2020-05-28 20:20:11	announced

Ibrahim AFM, Shen L, Tatham MH, Dickerson D, Prescott AR, Abidi N, Xirodimas DP, Hay RT, Antibody RING-Mediated Destruction of Endogenous Proteins. Mol Cell, 79(1):155-166.e9(2020) [pubmed]

submitter keyword: ARMeD Endogenous Protein Knockdown

Ron Hay
contact affiliation	University of Dundee
contact email	r.t.hay@dundee.ac.uk
lab head
David Dickerson
contact affiliation	University of Dundee
contact email	ddickerson@dundee.ac.uk
dataset submitter

Panorama Public dataset URI