Figure 8
From: Unique aspects of transcriptional regulation in neurons – nuances in NFκB and Sp1-related factors
Schematic for the roles of Sp1 and Sp4 in neuronal differentiation and degeneration. Immature neuroblasts appear to similar levels of Sp1 and Sp4, perhaps competing for regulatory control of genes not strongly related to differentiated neuronal function. After differentiation, mature neurons have much lower levels of Sp1; Sp4 competitively inhibits DNA binding and exerts transcriptional repression on genes related to mitosis and other genes inappropriate for neurons, such as ApoE. Upon excessive stimulation of glutamate receptors, a large calcium influx activates calpain, which digests Sp4. This may relieve the transcriptional repression of mitotic genes, permitting their inappropriate expression in terminally differentiated neurons; the latter appears sufficient to trigger apoptosis.