title: Harnessing the master transcriptional repressor REST to reciprocally regulate neurogenesis.
abstract: Neurogenesis begins in embryonic development and continues at a reduced rate into adulthood in vertebrate species, yet the signaling cascades regulating this process remain poorly understood. Plasma membrane-initiated signaling cascades regulate neurogenesis via downstream pathways including components of the transcriptional machinery. A nuclear factor that temporally regulates neurogenesis by repressing neuronal differentiation is the repressor element 1 (RE1) silencing transcription (REST) factor. We have recently discovered a regulatory site on REST that serves as a molecular switch for neuronal differentiation. Specifically, C-terminal domain small phosphatase 1, CTDSP1, present in non-neuronal cells, maintains REST activity by dephosphorylating this site. Reciprocally, extracellular signal-regulated kinase, ERK, activated by growth factor signaling in neural progenitors, and peptidylprolyl cis/trans isomerase Pin1, decrease REST activity through phosphorylation-dependent degradation. Our findings further resolve the mechanism for temporal regulation of REST and terminal neuronal differentiation. They also provide new potential therapeutic targets to enhance neuronal regeneration after injury.
authors.affiliation: Alcamena Stem Cell Therapeutics, LLC ; Beltsville, MD USA.
authors.forename: Edmund
authors.initials: E
authors.lastname: Nesti
keywords: CTDSP1; EGF; ERK; Pin1; RE1 silencing transcription factor; REST; astrocyte; brain injury; neuronal differentiation; βTrCP