Necdin is expressed predominantly in postmitotic neurons, and ectopic expression of this
protein strongly suppresses cell growth.
Necdin has been implicated in the pathogenesis of
Prader-Willi syndrome, a human
neurodevelopmental disorder associated with genomic imprinting. Here we demonstrate that ectopic expression of
necdin induces a neuronal phenotype in
neuroblastoma cells.
Necdin was undetectable in mouse
neuroblastoma N1E-115 cells under undifferentiated and differentiated conditions. N1E-115 cells transfected with
necdin cDNA showed morphological differentiation such as neurite outgrowth and expression of the synaptic marker
proteins synaptotagmin and
synaptophysin. In addition, Western blot analysis of the
retinoblastoma protein (Rb) family members Rb, p130, and p107 revealed that
necdin cDNA transfectants contained an increased level of p130 and a reduced level of p107, a pattern seen in differentiated G(0) cells. The
transcription factors E2F1 and E2F4 physically interacted with
necdin via their carboxyl-terminal transactivation domains, but only E2F1 abrogated
necdin-induced growth arrest and neurite outgrowth of
neuroblastoma cells. Overexpression of E2F1 in differentiated N1E-115 cells induced apoptosis, which was antagonized by co-expression of
necdin. These results suggest that
necdin promotes the differentiation and survival of neurons through its antagonistic interactions with E2F1.