PXD025338-1

PXD025338 is an original dataset announced via ProteomeXchange.

Title	ADAR1 interactome analysis, LC-MS/MS
Description	Adenosine-to-inosine (A-to-I) RNA editing catalyzed by ADAR1 plays essential roles in the regulation of diverse molecular and cellular processes both under physiological conditions and in the disease states, including cancer. However, mechanisms governing the protein abundance and activity of ADAR1, particularly of its constitutively-expressed and ubiquitous form, ADAR1p110, are largely unknown. Here, we report the E3 ubiquitin ligase SMURF2 as an essential positive regulator of ADAR1p110. We show that SMURF2 directly interacts with ADAR1p110, oligo-ubiquitinates it in an E3 ubiquitin ligase-dependent manner, and stabilizes ADAR1p110 expression by reducing its proteolysis through the proteasomal and lysosomal degradation pathways. The ability of SMURF2 to positively regulate ADAR1p110 was observed in different types of human cells and tissues, and in mouse tissues derived from Smurf2 knock-out and wild-type animals. Further investigations uncovered that SMURF2 regulates ADAR1p110 through its ubiquitination on K744 residue. Mutation of K744 to arginine (K744R), which is also linked to several human disorders, abolished SMURF2-mediated protection of ADAR1p110 from the proteolysis and inactivated its RNA editing activity. Additionally, SMURF2 showed a significant impact on ADAR1p110 protein-protein interactions, influencing its stability and functions. Altogether, these findings reveal SMURF2 as a multilayer regulator of ADAR1p110, governing its protein expression, interactions and functions.
HostingRepository	PRIDE
AnnounceDate	2022-05-29
AnnouncementXML	Submission_2022-05-29_09:33:20.156.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Praveen Koganti
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-12 20:05:13	ID requested
⏵ 1	2022-05-29 09:33:20	announced

Koganti P, Kadali VN, Manikoth Ayyathan D, Emanuelli A, Paolini B, Levy-Cohen G, Blank M, The E3 ubiquitin ligase SMURF2 stabilizes RNA editase ADAR1p110 and promotes its adenosine-to-inosine (A-to-I) editing function. Cell Mol Life Sci, 79(5):237(2022) [pubmed]

submitter keyword: Human embryonic kidney HEK-293T cells LC-MS/MS

Michael Blank
contact affiliation	Laboratory of Molecular and Cellular Cancer Biology, Azrieli Faculty of Medicine, Bar-Ilan University, 1311502 Safed, Israel.
contact email	michael.blank@biu.ac.il
lab head
Praveen Koganti
contact affiliation	The Azrieli Faculty of Medicine, Bar-Ilan University
contact email	kogantipraveen1@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025338
     1. Label: PRIDE project
     2. Name: ADAR1 interactome analysis, LC-MS/MS