PXD028114

PXD028114 is an original dataset announced via ProteomeXchange.

Title	RNA-binding proteins associating with the 3’UTR of the ATP6V1A transcript in SIRT1 knock-down cells
Description	Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) binds various RNA transcripts and functions as a tumor promoter, although little is known regarding the mechanisms that regulate its roles in RNA metabolism (1-3). Here we find that IGF2BP2 binds to the 3’ untranslated region of the transcript encoding ATP6V1A, a major catalytic subunit of the vacuolar ATPase (v-ATPase), and regulates its degradation in a lysine acetylation and SIRT1-dependent manner. We show that the regulation of IGF2BP2 is significantly compromised in breast cancer cells where SIRT1 expression is low or knocked-down. Reduced SIRT1 expression leads to an increase in acetylated IGF2BP2, which enables IGF2BP2 to recruit the XRN2 nuclease to the ATP6V1A transcript, resulting in its degradation and a reduction in the expression of functional v-ATPase complexes. This impairs lysosomal activity and produces a cellular secretome consisting of increased numbers of exosomes enriched in ubiquitinated protein cargo and soluble hydrolases including cathepsins, which combine to promote tumor progression and invasiveness. Collectively, these findings describe a previously unrecognized role for IGF2BP2 in mediating the degradation of an mRNA transcript essential for lysosomal function and highlight how its sirtuin-regulated acetylation state can have significant biological and disease consequences.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:40:34.838.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Elena Panizza
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-25 03:55:04	ID requested
1	2023-03-10 12:58:03	announced
⏵ 2	2023-11-14 07:40:37	announced	2023-11-14: Updated project metadata.

Latifkar A, Wang F, Mullmann JJ, Panizza E, Fernandez IR, Ling L, Miller AD, Fischbach C, Weiss RS, Lin H, Cerione RA, Antonyak MA, IGF2BP2 promotes cancer progression by degrading the RNA transcript encoding a v-ATPase subunit. Proc Natl Acad Sci U S A, 119(45):e2200477119(2022) [pubmed]

submitter keyword: breast cancer, SIRT1, RNA-binding proteins,human, ATP6V1A

Richard A. Cerione
contact affiliation	Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA Department of Molecular Medicine, Cornell University, Ithaca, New York 14853, USA
contact email	rac1@cornell.edu
lab head
Elena Panizza
contact affiliation	Cornell University
contact email	elena.panizza84@gmail.com
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/2023/03/PXD028114

PRIDE project URI

• PRIDE
  1. PXD028114
     1. Label: PRIDE project
     2. Name: RNA-binding proteins associating with the 3’UTR of the ATP6V1A transcript in SIRT1 knock-down cells