The N-terminal Set-β Protein Isoform Induces Neuronal Death.

Journal Article (Journal Article)

Set-β protein plays different roles in neurons, but the diversity of Set-β neuronal isoforms and their functions have not been characterized. The expression and subcellular localization of Set-β are altered in Alzheimer disease, cleavage of Set-β leads to neuronal death after stroke, and the full-length Set-β regulates retinal ganglion cell (RGC) and hippocampal neuron axon growth and regeneration in a subcellular localization-dependent manner. Here we used various biochemical approaches to investigate Set-β isoforms and their role in the CNS, using the same type of neurons, RGCs, across studies. We found multiple alternatively spliced isoforms expressed from the Set locus in purified RGCs. Set transcripts containing the Set-β-specific exon were the most highly expressed isoforms. We also identified a novel, alternatively spliced Set-β transcript lacking the nuclear localization signal and demonstrated that the full-length (∼39-kDa) Set-β is localized predominantly in the nucleus, whereas a shorter (∼25-kDa) Set-β isoform is localized predominantly in the cytoplasm. Finally, we show that an N-terminal Set-β cleavage product can induce neuronal death.

Full Text

Duke Authors

Cited Authors

  • Trakhtenberg, EF; Morkin, MI; Patel, KH; Fernandez, SG; Sang, A; Shaw, P; Liu, X; Wang, Y; Mlacker, GM; Gao, H; Velmeshev, D; Dombrowski, SM; Vitek, MP; Goldberg, JL

Published Date

  • May 22, 2015

Published In

Volume / Issue

  • 290 / 21

Start / End Page

  • 13417 - 13426

PubMed ID

  • 25833944

Pubmed Central ID

  • PMC4505589

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

Digital Object Identifier (DOI)

  • 10.1074/jbc.M114.633883


  • eng

Conference Location

  • United States