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PXD010484-1

PXD010484 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA complex containing lysine-acetylated actin inhibits the formin INF2
DescriptionINF2 is a member of the formin family of actin assembly factors. Dominant mis-sense mutations in INF2 link to two diseases: focal segmental glomerulosclerosis (FSGS), a kidney disease; and Charcot-Marie-Tooth disease (CMTD), a neuropathy. All disease mutations map to the autoinhibitory Diaphanous Inhibitory Domain (DID). Curiously, purified INF2 is not autoinhibited, suggesting the existence of additional cellular inhibitors. We purified an INF2 inhibitor from mouse brain, and identified it as a complex between lysine-acetylated actin (KAc-actin) and cyclase-associated protein (CAP). Inhibition of INF2 by CAP/KAc-actin requires INF2 DID. Treatment of CAP/KAc-actin with histone deacetylase 6 (HDAC6) releases INF2 inhibition, while HDAC6 inhibitors block cellular INF2 activation. INF2 disease mutants are poorly inhibited by CAP/KAc-actin, suggesting that FSGS and CMTD result from reduced CAP/KAc-actin binding. This is the first demonstrated role for lysine-acetylated actin: regulation of an actin assembly factor by a novel mechanism, which we call facilitated auto-inhibition.
HostingRepositoryMassIVE
AnnounceDate2019-01-30
AnnouncementXMLSubmission_2019-01-30_11:27:39.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterMark Adamo
SpeciesList scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationListCarbamidomethyl; Oxidation
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-07-18 13:39:43ID requested
12019-01-30 11:27:40announced
Publication List
Mu A, Tak Shun Fung, Arminja N. Kettenbach, Rajarshi Chakrabarti, Henry Higgs. A complex containing lysine-acetylated actin inhibits the formin INF2. .
Keyword List
submitter keyword: INF2, actin, FSGS, CMTD, DID, CAP, Ac-actin, HDAC6, autoinhibition, formin
Contact List
Arminja Kettenbach
contact affiliationThe Geisel School of Medicine at Dartmouth
contact emailarminja.n.kettenbach@dartmouth.edu
lab head
Mark Adamo
contact affiliationDartmouth College
contact emailmark.e.adamo@dartmouth.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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