Faculty Bibliography

The three-dimensional structure of the basic/helix-loop-helix/leucine zipper domain of the transcription factor Max complexed with DNA has been determined by X-ray crystallography at 2.9 A resolution. Max binds as a dimer to its recognition sequence CACGTG by direct contacts between the alpha-helical basic region and the major groove. This symmetric homodimer, a new protein fold, is a parallel, left-handed, four-helix bundle, with each monomer containing two alpha-helical segments separated by a loop. The two alpha-helical segments are composed of the basic region plus helix 1 and helix 2 plus the leucine repeat, respectively. As in GCN4, the leucine repeat forms a parallel coiled coil

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