TI - The Bax N terminus regulates inhibition by Bcl-xL . AB - Since Bcl-xL poorly regulated Bax 30-146 or 30-192 despite the association with the protein , we tested if the N-terminus can modulate this function . Apoptosis triggered by Bax 1-146 which includes the N-terminus and the TM1 domain was efficiently blocked by RFP-Bcl-xL (Figure 7A) . Bax 1-146 immunoprecipitates Bcl-xL and is detected in both mitochondrial and cytosolic fractions ( Figure 7B ) . Furthermore , the punctate distribution of Bax 1-146 in apoptotic cells redistributes to a diffuse pattern in cells that co-express Bcl-xL (Figure 7C) . The distribution of Bax 1-146 overlaps significantly with that of Bcl-xL (Figure 7C) . The change in distribution of Bax 1-146 in response to co-expressed Bcl-xL is shown ( Figure 7D ) . In a construct that lacks the TM domains , the N-terminus did not modulate Bax-BH3 function (Figure 7E) . PHOSphorylation dependent modifications that change protein conformation regulate the apoptotic function of Bcl-2 family proteins . Bax-induced apoptosis is inhibited by the serine-threonine kinase Akt ( Figure 7F and 7H ) . This regulation was compromised in a Bax construct ( Bax-Ala3 ) with alanine substitutions of the Ser/Thr residues ( Thr14 , Ser15 , Ser16 ) in the N-terminus which was refractory to inhibition by Akt ( Figure 7F and 7H ) . The modification in the N-terminus however , did not interfere with Bcl-xL inhibition of Bax-Ala3 induced apoptosis ( Figure 7G and 7I ) .