PXD026554

PXD026554 is an original dataset announced via ProteomeXchange.

Title	Ubiquitination at the Parkin ubiquitin-like domain suggests a new mechanism for Parkin activation
Description	The mitochondrial kinase PINK1 and the cytosolic ubiquitin ligase (E3) Parkin is involved in mitochondrial quality control. PINK1, which phosphorylates ubiquitin at serine 65 residue and the ubiquitin-like (Ubl) domain of Parkin at serine 65 residue, promotes the Parkin activation and translocation to damaged mitochondria. When Parkin is activated, the Ubl domain are ubiquitinated at lysine 27 (K27) and lysine 48 (K48) residues. It remains unclear whether K27/K48 ubiquitination contributes to Parkin activity. In this study, we blocked the ubiquitination of K27 and/or K48 residues to examine the effects of the Parkin Ubl ubiquitination in Drosophila. Parkin replaced K27 with arginine (K27R) rescued the lethality of flies by PINK1 and Parkin co-expression whereas K48 replacement with arginine did not. Parkin K27R exhibited less ability of mitochondrial fragmentation and mitochondrial arrest, which are mediated by the degradation of Parkin E3 substrates Mitofusin and Miro, respectively. The pathogenic K27N Parkin, unlike K27R Parkin, was found to be completely devoid of E3 activity, suggesting not only that K27N Parkin is not ubiquitin-modified at the K27 residue but also that the structure of the Ubl domain itself is largely affected. Ubiquitin attached to the K27 residue of the Ubl domain during PINK1-mediated Parkin activation was likely to be phosphorylated because K27R Parkin showed less ability of Parkin self-association upon the reduction of the mitochondrial membrane potential. Our study suggests a new Parkin activation mechanism where an activating complex for Parkin is formed through phospho-ubiquitin attached to the K27 residue of the Ubl domain.
HostingRepository	jPOST
AnnounceDate	2022-08-24
AnnouncementXML	Submission_2022-09-18_02:23:56.451.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD026554
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Kosuke Ogata
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-carboxamidomethyl-L-cysteine; O4'-phospho-L-tyrosine; O-phospho-L-threonine; O-phospho-L-serine; ubiquitination signature dipeptidyl lysine
Instrument	TripleTOF 5600; instrument

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-07 22:28:38	ID requested
1	2022-08-23 19:05:08	announced
⏵ 2	2022-09-18 02:23:57	announced	2022-09-18: Updated FTP location.

Liu JY, Inoshita T, Shiba-Fukushima K, Yoshida S, Ogata K, Ishihama Y, Imai Y, Hattori N, Ubiquitination at the lysine 27 residue of the Parkin ubiquitin-like domain is suggestive of a new mechanism of Parkin activation. Hum Mol Genet, 31(15):2623-2638(2022) [pubmed]

submitter keyword: ubiquitin

PTEN-induced kinase 1

parkin

phosphorylation

Parkinson disease

Drosophila genetics

neuron

Nobutaka Hattori
lab head
Kosuke Ogata
contact affiliation	Kyoto university
dataset submitter

jPOST dataset URI

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.jpostdb.org/JPST001210/