page 985 by Chittka et al.
NGF is a neuronal survival and differentiation factor expressed in the developing nervous system. NGF binds to two different classes of receptors: the TrkA tyrosine kinase receptor and p75NTR. While studying how p75NTR functions in NGF signaling, Chittka and colleagues had previously shown that this receptor interacts with SC1, a zinc finger protein that moves to the nucleus in response to NGF.
The group now shows that SC1 is a transcriptional repressor that halts proliferation in cultured cells. NGF activates the repressor, which complexes in the nucleus with histone deacetylases. At least part of the reason for the cell cycle block is that SC1 turns off cyclin E transcription, thus preventing entry into S phase. SC1's repressive activity is enhanced by both TrkA and p75NTR, although physical interaction with SC1 has only been shown for p75NTR.
Other genes are probably also repressed by SC1, and the authors hope that upcoming microarray experiments will identify many of them. Chittka suspects that genes that are unnecessary in neural lineages will be among those turned off by SC1. In this way, SC1 could coordinate the onset of differentiation with the last mitotic cycle of precursor cells. ▪