PXD021789-1

PXD021789 is an original dataset announced via ProteomeXchange.

Title	The AMBRA1 E3 ligase adaptor regulates Cyclin D protein stability
Description	Here we describe AMBRA1 as the main regulator of Cyclin D protein degradation. We first identify AMBRA1 as the top candidate in a genome-wide CRISPR/Cas9 loss-of-function screen investigating the genetic basis of resistance to chemical CDK4/6 inhibition. AMBRA1 loss results in high protein levels of Cyclin D in cells and in mice. AMBRA1 loss further promotes lung cancer development in a mouse model, and low levels of AMBRA1 correlate with worse survival in lung cancer patients. Mechanistically, AMBRA1 acts as a substrate receptor for the Cullin 4 E3 ligase complex to promote ubiquitylation and proteasomal degradation of the three Cyclin D family members. Thus, AMBRA1 regulates Cyclin D protein levels and contributes to the development of cancer as well as the response of cancer cells to CDK4/6 inhibitors.
HostingRepository	PRIDE
AnnounceDate	2021-07-24
AnnouncementXML	Submission_2021-07-24_11:45:49.636.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD021789
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Janos Demeter
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-02 04:14:56	ID requested
⏵ 1	2021-07-24 11:45:50	announced

Chaikovsky AC, Li C, Jeng EE, Loebell S, Lee MC, Murray CW, Cheng R, Demeter J, Swaney DL, Chen SH, Newton BW, Johnson JR, Drainas AP, Shue YT, Seoane JA, Srinivasan P, He A, Yoshida A, Hipkins SQ, McCrea E, Poltorack CD, Krogan NJ, Diehl JA, Kong C, Jackson PK, Curtis C, Petrov DA, Bassik MC, Winslow MM, Sage J, D. Nature, 592(7856):794-798(2021) [pubmed]

submitter keyword: Human, Cell cycle, Cyclin D, cancer

Julien Sage
contact affiliation	Departments of Pediatrics and Genetics, Stanford University, Stanford, CA, USA.
contact email	julsage@stanford.edu
lab head
Janos Demeter
contact affiliation	Stanford University
contact email	jdemeter@stanford.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/2021/07/PXD021789

PRIDE project URI

• PRIDE
  1. PXD021789
     1. Label: PRIDE project
     2. Name: The AMBRA1 E3 ligase adaptor regulates Cyclin D protein stability