Figure 7.

Potential relationships between IMPD and putative mediators of p53-dependent growth suppression. The left branch of the flow diagram depicts IMPD in its role as a rate-determining mediator of p53-dependent growth suppression in the absence of cellular damage. Reduced IMPD activity in response to p53 expression is obligatory for p53-dependent growth suppression under normal growth conditions. This experimental response is proposed to reflect a physiological response to variation in growth factor levels or other tissue factors in vivo that serves to modulate the levels of a critical guanine ribonucleotide(s) (rGNPs) required for cell cycle progression. These studies call into question the presumed role of bax and waf1 as induced mediators of p53-dependent growth suppression. This apparent conflict may be resolved by a restriction of bax and waf1 function to states of DNA damage or by a dependence of their function on guanine ribonucleotides regulated by IMPD.