Consistent with the observation that the nuclear localization of Sp1 was enhanced through activation of the PI3K-Akt pathway in MM cells under acidic conditions (Figure 3A), the PI3K inhibitor LY294002 restored DR4 expression in MM cells suppressed at pH6.8 at protein as well as mRNA levels (Figure 6C), suggesting that DR4 repression in MM cells under acidic conditions is largely mediated by activation of the PI3K-Akt-Sp1 pathway. The gene discussed is TNFRSF10A; the disease is Miyoshi myopathy.