Cell Biology

p75 Goes Nuclear

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Science  12 Mar 2010:
Vol. 327, Issue 5971, pp. 1303-1305
DOI: 10.1126/science.327.5971.1303-d
CREDIT: PARKHURST ET AL., J. BIOL. CHEM. 285, 5361 (2010)

The p75 neurotrophin receptor binds to all members of the neurotrophin family, which promote differentiation, growth, and survival of diverse cell types in the nervous system. On its own, p75 can also produce signals, which appear to require its proteolysis by a presenilin-dependent γ-secretase. In the case of the receptor Notch, such cleavage produces an intracellular domain (ICD) fragment that moves to the nucleus to regulate gene expression. Parkhurst et al. present evidence that the p75 ICD may similarly regulate gene expression. A fusion protein was produced with p75 linked to a transcriptional activator that would cause expression of green fluorescent protein (GFP) if the cleaved fragment of the receptor reached the nucleus. Production of GFP was indeed detected in human cells transfected with the receptor construct, which was prevented by inhibition of γ-secretase. In PC12 cells (a cell line with neuronal characteristics), the endogenous p75 protein ICD fragment was detected in the nucleus. Furthermore, the p75 ICD associated with the promoter of the cyclin E1 gene when PC12 cells were treated with nerve growth factor for 3 hours. The ICD can interact with multiple intracellular proteins and may thus influence numerous signaling events. Thus, a primary action of the p75 ICD (and possibly fragments of the related receptors) may be direct regulation of transcription in the nucleus.

J. Biol. Chem. 285, 5361 (2010).

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