EXPRESSION OF TRANSCRIPTIONAL REPRESSOR PROTEIN MSIN3A BUT NOT MSIN3BIS INDUCED DURING NEURONAL APOPTOSIS

mSin3 proteins have an important role in transcriptional repression me diated by histone deacetylation. Our purpose was to find out whether a poptosis affects the expression of mSin3 proteins in neuroblastoma 2a cells. We observed that neuronal apoptosis, induced by serum withdrawa l or by treatment with etoposide, okadaic acid or trichostatin A, indu ced a prominent increase in mSin3A protein expression but did not affe ct the level of mSin3B protein. Trichostatin A, an inhibitor of histon e deacetylases, induced the most prominent upregulation of mSin3A prot ein. Metabolic labeling and immunoprecipitation of mSin3A showed a mar ked increase in the synthesis of mSin3A protein in agreement with the immunoblotting results. Interestingly, the expression of mSin3A preced ed the activation of caspase-3 and the execution phase of neuronal apo ptosis. These results suggest that the expression of mSin3A proteins m ay provide a regulation mechanism to enhance transcriptional repressio n or silencing of genes during neuronal apoptosis, as well as during d egenerative diseases. (C) 1998 Academic Press.