Dataset Information

C-terminal Domain Small Phosphatase 1 and MAP kinase reciprocally control REST stability and neuronal differentiation.

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Rattus Norvegicus (rat)

SUBMITTER: Phillip Wilmarth

LAB HEAD: Gail Mandel

PROVIDER: PXD001127 | Pride | 2014-09-15

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	2B_tryp_gluc_aspN_no_enzyme.sfd	Other
	MAN427_2B_20080410_LT.RAW	Raw
	MAN427_2B_gluC_20080420_LT3.RAW	Raw
	MAN456_2B_20080618_LT.RAW	Raw

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Publications

C-terminal domain small phosphatase 1 and MAP kinase reciprocally control REST stability and neuronal differentiation.

Nesti Edmund E Corson Glen M GM McCleskey Maxwell M Oyer Jon A JA Mandel Gail G

Proceedings of the National Academy of Sciences of the United States of America 20140902 37

The repressor element 1 (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 beta-transducin repeat containing E3 ubiquitin protein ligase, βTrCP. We identify ...[more]

PMID: 25197063

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