Adenovirus 5 E1A proteins disrupt the neuronal phenotype and growth factor responsiveness of PC12 cells by a conserved region 1-dependent mechanism

Abstract

Expression in PC12 cells of adenovirus 5 E1a proteins dramatically changes cell morphology and disrupts neuronal differentiation. We demonstrate that the nerve growth factor (NGF) receptors, p140trk and p75NGFR, as well as the epidermal growth factor receptor are undetectable in E1a-expressing PC12 cells. This correlates with a repression of mRNAs for the chromaffin- and neuronal-specific proteins, tyrosine hydroxylase and peripherin, while more ubiquitously expressed genes remain unaffected. One possible mechanism of E1a action could thus be the repression of a coordinately regulated group of chromaffin- and/or neuronal-specific genes. Furthermore, we show taht E1a conserved region 1, which binds p105Rb and p300, is necessary for this E1a-dependent effect. This indicates that cellular proteins interacting with E1a conserved region 1 may be implicated in growth arrest, expression of neuron-specific functions and orderly differentiation of PC12 cells in response to NGF.