PXD037793

PXD037793 is an original dataset announced via ProteomeXchange.

Title	Identification of SENP3 and SENP5 target proteins by endogenous SUMO2/3 IP-MS
Description	Ribosome biogenesis is a complex and energy demanding process requiring tight coordination with cell growth and proliferation. Impairment of ribosome biogenesis activates a well-defined cell-cycle checkpoint that primarily relies on the activation of p53 signaling. However, there is mounting evidence that p53-independent signaling networks connect impaired ribosome biogenesis to cell cycle-checkpoints. So far, however, these pathways have remained largely enigmatic. By characterizing the nucleolar SUMO isopeptidase SENP3 and SENP5 we found that both isopeptidases control the SUMOylation state of specific ribosome biogenesis factors and regulate the 60S and 40S ribosome maturation pathways. Accordingly, inactivation of SENP3 and SENP5 induces a canonical p53-mediated G1/S arrest. Intriguingly, however, we discovered that inactivation of SENP3 or SENP5 drastically and specifically downregulates the expression of the key-cell cycle regulator CDK6 in a p53-independent process. Accordingly, depletion of SENP3 or SENP5 impairs G1/S transition and cell proliferation in both p53-proficient and p53-deficient cells. Strikingly, we further revealed that impaired ribosome maturation induced by depletion of a panel of ribosome biogenesis factors or by chemical inhibition of RNA polymerase I, generally triggers loss of CDK6 independent of the cellular p53 status. Altogether our data unveil a long-sought p53-independent checkpoint of impaired ribosome biogenesis. Since CDK6 represents a dependency in a subset of cancer entities, such as AML and lymphoma, we propose that this checkpoint can serve as an actionable drug target in tumor therapy.
HostingRepository	PRIDE
AnnounceDate	2023-10-28
AnnouncementXML	Submission_2023-10-28_09:54:36.189.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	StefanMüller
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-28 02:31:00	ID requested
⏵ 1	2023-10-28 09:54:36	announced

Dataset with its publication pending

submitter keyword: SUMO, human, SENP, LC-MS/MS

StefanMüller
contact affiliation	IBCII, Goethe University Frankfurt, Germany, Medical School
contact email	ste.mueller@em.uni-frankfurt.de
lab head
StefanMüller
contact affiliation	Institute of Biochemistry II University Hospital Building 75 Theodor-Stern-Kai 7 60590 Frankfurt (Main)
contact email	ag-mueller@gmx.de
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/2023/10/PXD037793

PRIDE project URI

• PRIDE
  1. PXD037793
     1. Label: PRIDE project
     2. Name: Identification of SENP3 and SENP5 target proteins by endogenous SUMO2/3 IP-MS