PMID: 8939705Nov 1, 1996Paper

Specific inhibition of the chymotrypsin-like activity of the proteasome induces a bipolar morphology in neuroblastoma cells

Chemistry & Biology
G Fenteany, S L Schreiber

Abstract

Lactacystin inhibits cell proliferation and induces a distinctive, predominantly bipolar (two-neurite-bearing) morphology in Neuro 2A murine neuroblastoma cells. It binds with high specificity to the multicatalytic 20S proteasome and inhibits at least three of its peptidase activities (chymotrypsin-like, trypsin-like and peptidylglutamyl-peptide hydrolyzing), each at a different rate, without inhibiting other known proteases. The chymotrypsin-like and trypsin-like activities of the proteasome are inhibited most rapidly, and irreversibly. In an effort to determine which of the peptidase activities needs to be inhibited for neurite outgrowth to occur, we treated Neuro 2A cells with peptide aldehydes that selectively inhibit different proteasome activities. Treatment with peptide aldehydes ending in a hydrophobic residue, all of which inhibit the chymotrypsin-like activity, results in a bipolar morphology in Neuro 2A cells, whereas treatment with a peptide aldehyde inhibitor of the trypsin-like activity does not lead to a detectable change in morphology. One of the inhibitors that induces neurite outgrowth has been previously shown to inhibit the chymotrypsin-like activity of the proteasome without inhibiting the other apparently ...Continue Reading

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Citations

Mar 24, 2007·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Amalia MilanoFrancesco Caponigro
Oct 24, 2006·Current Problems in Surgery·Elizabeth A MittendorfMichael J Demeure
Feb 5, 2014·Protein Expression and Purification·Nilanjana BhattacharjeeSamir K Dutta
Jun 14, 2012·Neurochemistry International·Ajay S UnnithanRehana K Leak
Aug 31, 2006·Journal of Neuroscience Research·Pascal Kienlen-CampardJean-Noël Octave
May 16, 1998·The Journal of Biological Chemistry·G Fenteany, S L Schreiber
Sep 10, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xao X TangNaohiko Ikegaki
Sep 28, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Manisha H ShahMichael Grever

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