Figure 10.

Five phosphorylation changes mediate NPM toxicity during ischemic stress. Based on the results of our NPM bioassays (Figure 5), we propose that phosphorylation changes at S88 and T95^40,41 regulate steps 1–3 in the nucleophosmin-Bax cell death pathway. T95 phosphorylation also regulates cell death in response to chemotherapy and radiation therapy in acute myelogenous leukemia.^40,41 Release from nucleolar binding sites is assumed to occur before NPM deoligomerization or cytosolic translocation.^45,75 The function of NPM-T86, T234, and S242 phosphorylation changes during ischemic cell death is presently unknown.