PXD001127

PXD001127 is an original dataset announced via ProteomeXchange.

Title	C-terminal Domain Small Phosphatase 1 and MAP kinase reciprocally control REST stability and neuronal differentiation.
Description	The RE1 Silencing Transcription Factor (REST) in stem cells represses hundreds of genes essential to neuronal function. During neurogenesis, REST is degraded in neural progenitors to promote subsequent elaboration of a mature neuronal phenotype. Prior studies indicate that part of the degradation mechanism involves phosphorylation of two sites in the C-terminus of REST that require activity of the E3 ubiquitin ligase, bTrCP. We identify a new proline-directed phosphorylation motif, at Serines 861/864 upstream of these sites, which is a substrate for the Peptidyl-prolyl cis-trans Isomerase, Pin1, as well as the ERK1/2 kinases. Mutation at S861/864 stabilizes REST, as does inhibition of Pin1 activity. Interestingly, we find that C-Terminal Domain Small Phosphatase1 (CTDSP1) is recruited by REST to neuronal genes, is present in REST immunocomplexes, dephosphorylates S861/864 and stabilizes REST. Expression of a REST peptide containing S861/864 in neural progenitors inhibits terminal neuronal differentiation. Together with previous work indicating that both REST and CTDSP1 are expressed to high levels in stem cells and down regulated during neurogenesis, our results suggest that CTDSP1 activity stabilizes REST in stem cells, and that ERK dependent phosphorylation combined with Pin1 activity promotes REST degradation in neural progenitors.
HostingRepository	PRIDE
AnnounceDate	2014-09-15
AnnouncementXML	Submission_2014-09-15_00:53:22.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	phosphorylated residue
Instrument	LTQ

Revision	Datetime	Status	ChangeLog Entry
0	2014-07-11 01:07:07	ID requested
⏵ 1	2014-09-15 00:53:23	announced

Nesti E, Corson GM, McCleskey M, Oyer JA, Mandel G, C-terminal domain small phosphatase 1 and MAP kinase reciprocally control REST stability and neuronal differentiation. Proc Natl Acad Sci U S A, 111(37):E3929-36(2014) [pubmed]

curator keyword: Biomedical, Biological

submitter keyword: RE1 Silencing Transcription Factor, REST, bTrCP, CTDSP1, Pin1, ERK, neuronal differentiation.

Gail Mandel
contact affiliation	Vollum Inst., OHSU
contact email	mandelg@ohsu.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001127
     1. Label: PRIDE project
     2. Name: C-terminal Domain Small Phosphatase 1 and MAP kinase reciprocally control REST stability and neuronal differentiation.