WHAT INITIATES GENE EXPRESSION AT CONTACT INHIBITION?
Immediate phosphatase inactivation of mitogenic signaling at contact inhibition likely leads to expression of some genes. However, additional transcriptional mechanisms are emerging. C/EBP (CCAAT/enhancer-binding protein) transcription factors are important in the differentiation and function of many tissues54. Two reports have shown that certain C/EBP isoforms are upregulated at contact inhibition in specific cells: C/EBP- and C/EBP- in mammary epithelial cells and NIH3T3 cells, respectively55, and C/EBP- in chicken embryo fibroblasts56. Although transcriptional targets were not identified for C/EBP- and C/EBP-, antisense RNA inhibition of C/EBP- expression delayed growth arrest55. However, a C/EBP- targeted “quiescence-responsive unit” was mapped in the GAS gene, p20K, raising the possibility that similar sequences may exist in the promoters of other genes activated by contact inhibition56. Yet, an enigma remains: Given that C/EBP isoforms are themselves transcriptionally activated b