PXD018329

PXD018329 is an original dataset announced via ProteomeXchange.

Title	Quantitative proteomics in G1 cells reveals the insulin receptor adaptor IRS2 as an APC/CCdh1 substrate
Description	The anaphase promoting complex/cyclosome (APC/C) is a ubiquitin ligase that controls progression through the eukaryotic cell cycle by targeting key substrates for degradation through the ubiquitin proteasome pathway. During G1, the APC/C works in concert with its co-activator Cdh1 to recognize and ubiquitinate specific substrates during this phase of the cell cycle. While many APC/CCdh1 substrates play a role cell cycle regulation, others are involved in distinct cellular processes, indicating that diverse biological pathways are subject to APC/C-mediated control. To identify novel pathways and substrates regulated by APC/CCdh1, we conducted an unbiased proteomic screen in G1-arrested RPE1 cells acutely treated with small molecule APC/C inhibitors. Combining these results with degron prediction analysis, we discovered a range of putative APC/C substrates. We validated IRS2, a key adaptor protein involved in signaling downstream of the insulin and IGF1 receptors, as a novel direct APC/CCdh1 target. We demonstrate that genetic deletion of IRS2 reduces the expression of proteins involved in cell division and functionally impairs the spindle assembly checkpoint. Together, these findings reveal a novel connection between the insulin/IGF1 signaling network and the cell cycle regulatory machinery.
HostingRepository	PRIDE
AnnounceDate	2020-06-22
AnnouncementXML	Submission_2020-06-21_22:17:22.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD018329
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Qing Yu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex; Oxidation; Carbamidomethyl
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-01 22:23:09	ID requested
⏵ 1	2020-06-21 22:17:23	announced

Manohar S, Yu Q, Gygi SP, King RW, The Insulin Receptor Adaptor IRS2 is an APC/C Substrate That Promotes Cell Cycle Protein Expression and a Robust Spindle Assembly Checkpoint. Mol Cell Proteomics, 19(9):1450-1467(2020) [pubmed]

submitter keyword: IRS2, TMT, APC substrate, human

Steven P Gygi
contact affiliation	Harvard Medical School
contact email	steven_gygi@HMS.HARVARD.EDU
lab head
Qing Yu
contact affiliation	Harvard Medical School
contact email	qing_yu2@hms.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018329
     1. Label: PRIDE project
     2. Name: Quantitative proteomics in G1 cells reveals the insulin receptor adaptor IRS2 as an APC/CCdh1 substrate