Nuclear proteasomal degradation and cytoplasmic retention underlie early nuclear exclusion of transcription factor Max upon axon damage.

The behavior of the transcription factor Max in axon-damaged retinal ganglion cells (RGC) was investigated in explants from the rat retina, used as a tissue culture model of the central nervous system (CNS). Axon damage leads to an apparent rapid shift in the localization of Max from the nucleus to the cytoplasm, in advance of markers of apoptosis. This nuclear exclusion resisted treatments with calpeptin or the CRM1 exportin inhibitor leptomycin B, but was prevented by low temperature. Inhibition of either transcription or translation prevented RGC death, but only the latter robustly prevented nuclear exclusion. The proteasome inhibitor lactacystin prevented nuclear exclusion, whereas newly synthesized Max still accumulated in the cytoplasm of the axon-damaged RGC. The results show that proteosomal degradation of nuclear Max coupled with continued expression and cytoplasmic accumulation of Max, with blockade of nucleocytoplasmic transport of the newly synthesized protein, is an early event after CNS axonal damage.

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