Protein Palmitoylation Regulates Neural Stem Cell Differentiation by Modulation of EID1 Activity

Mol Neurobiol. 2016 Oct;53(8):5722-36. doi: 10.1007/s12035-015-9481-y. Epub 2015 Oct 26.

Abstract

The functional significance of palmitoylation in the switch between self-renewal and differentiation of neural stem cells (NSCs) is not well defined, and the underlying mechanisms of protein palmitoylation are not well understood. Here, mouse NSCs were used as a model system and cell behavior was monitored in the presence of the protein palmitoylation inhibitor 2-bromopalmitate (2BRO). Our data show that 2BRO impaired the differentiation of NSCs into both neurons and glia and impaired NSC cell cycle exit. Moreover, the results show that palmitoylation modified E1A-like inhibitor of differentiation one (EID1) and this modification regulated EID1 degradation and CREB-binding protein (CBP)/p300 histone acetyltransferase activity at the switch between self-renewal and differentiation of NSCs. Our results extended the cellular role of palmitoylation, suggesting that it acts as a regulator in the acetylation-dependent gene expression network, and established the epigenetic regulatory function of palmitoylation in the switch between maintenance of multipotency and differentiation in NSCs.

Keywords: 2-bromopalmitate; CBP/p300; EID1; Mouse NSCs; Palmitoylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Acyltransferases / antagonists & inhibitors
  • Acyltransferases / metabolism
  • Amino Acid Sequence
  • Animals
  • CREB-Binding Protein / metabolism
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Differentiation* / drug effects
  • Cell Differentiation* / genetics
  • Cell Proliferation / drug effects
  • Cell Self Renewal / drug effects
  • Cell Self Renewal / genetics
  • E1A-Associated p300 Protein / metabolism
  • Gene Expression Regulation / drug effects
  • Histones / metabolism
  • Lipoylation*
  • Mice
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / ultrastructure
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Palmitates / pharmacology
  • Proteolysis / drug effects
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism*
  • Subcellular Fractions / metabolism
  • Transcription, Genetic / drug effects

Substances

  • EID1 protein, mouse
  • Histones
  • Nuclear Proteins
  • Palmitates
  • Repressor Proteins
  • 2-bromopalmitate
  • Acyltransferases
  • CREB-Binding Protein
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse