{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:03:53Z","timestamp":1791187433257,"version":"4.1.0"},"reference-count":73,"publisher":"Society for Neuroscience","issue":"21","license":[{"start":{"date-parts":[[2014,11,21]],"date-time":"2014-11-21T00:00:00Z","timestamp":1416528000000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2014,5,21]]},"abstract":"<jats:p>\n                    The failure of the CNS neurons to regenerate axons after injury or stroke is a major clinical problem. Transcriptional regulators like Set-\u03b2 are well positioned to regulate intrinsic axon regeneration capacity, which declines developmentally in maturing CNS neurons. Set-\u03b2 also functions at cellular membranes and its subcellular localization is disrupted in Alzheimer's disease, but many of its biological mechanisms have not been explored in neurons. We found that Set-\u03b2 was upregulated postnatally in CNS neurons, and was primarily localized to the nucleus but was also detected in the cytoplasm and adjacent to the plasma membrane. Remarkably, nuclear Set-\u03b2 suppressed, whereas Set-\u03b2 localized to cytoplasmic membranes promoted neurite growth in rodent retinal ganglion cells and hippocampal neurons. Mimicking serine 9 phosphorylation, as found in Alzheimer's disease brains, delayed nuclear import and furthermore blocked the ability of nuclear Set-\u03b2 to suppress neurite growth. We also present data on gene regulation and protein binding partner recruitment by Set-\u03b2 in primary neurons, raising the hypothesis that nuclear Set-\u03b2 may preferentially regulate gene expression whereas Set-\u03b2 at cytoplasmic membranes may regulate unique cofactors, including PP2A, which we show also regulates axon growth\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Finally, increasing recruitment of Set-\u03b2 to cellular membranes promoted adult rat optic nerve axon regeneration after injury\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Thus, Set-\u03b2 differentially regulates axon growth and regeneration depending on subcellular localization and phosphorylation.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.3658-13.2014","type":"journal-article","created":{"date-parts":[[2014,5,21]],"date-time":"2014-05-21T13:05:00Z","timestamp":1400677500000},"page":"7361-7374","source":"Crossref","is-referenced-by-count":42,"title":["Regulating Set-\u03b2's Subcellular Localization Toggles Its Function between Inhibiting and Promoting Axon Growth and Regeneration"],"prefix":"10.1523","volume":"34","author":[{"given":"Ephraim F.","family":"Trakhtenberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina I.","family":"Morkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie 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