JNK-dependent Phosphorylation of c-Jun on Serine 63 Mediates Nitric Oxide-induced Apoptosis of Neuroblastoma Cells

c-Jun NH2-terminal kinases (JNKs) potentiate transcriptional activity of c-Jun by phosphorylating serines 63 and 73. Moreover, JNK and c-Jun can modulate apoptosis. However, an involvement of nitric oxide (NO)-induced phosphorylation of c-Jun on Ser-63 and Ser-73 in apoptosis has not been explored. We report that in SH-Sy5y neuroblastoma cells, NO induced apoptosis following JNK activation and phosphorylation of c-Jun almost exclusively on Ser-63. Importantly, NO-induced apoptosis and caspase-3 activity were inhibited in cells stably transformed with dominant-negative c-Jun in which Ser-63 is mutated to alanine (S63A), but not in cells transformed with dominant-negative c-Jun (S73A). Ser-63 of c-Jun (but not Ser-73) was required for NO-induced, c-Jun-dependent transcriptional activity. NO-induced apoptosis, Ser-63 phosphorylation of c-Jun, and caspase-3 activity were all inhibited in SH-Sy5y cells transformed with dominant-negative jnk. A caspase-3 inhibitor prevented apoptosis but not c-Jun phosphorylation. In neuroblastoma NO-induced Ser-63 phosphorylation of c-Jun and apoptosis were by JNK We that apoptosis is by Ser-63 phosphorylation of c-Jun of caspase-3 activation in neuroblastoma c-Jun NH2-terminal kinases (JNKs) potentiate transcriptional activity of c-Jun by phosphorylating serines 63 and 73. Moreover, JNK and c-Jun can modulate apoptosis. However, an involvement of nitric oxide (NO)-induced phosphorylation of c-Jun on Ser-63 and Ser-73 in apoptosis has not been explored. We report that in SH-Sy5y neuroblastoma cells, NO induced apoptosis following JNK activation and phosphorylation of c-Jun almost exclusively on Ser-63. Importantly, NO-induced apoptosis and caspase-3 activity were inhibited in cells stably transformed with dominant-negative c-Jun in which Ser-63 is mutated to alanine (S63A), but not in cells transformed with dominant-negative c-Jun (S73A). Ser-63 of c-Jun (but not Ser-73) was required for NO-induced, c-Jun-dependent transcriptional activity. NO-induced apoptosis, Ser-63 phosphorylation of c-Jun, and caspase-3 activity were all inhibited in SH-Sy5y cells transformed with dominant-negative jnk. A caspase-3 inhibitor prevented apoptosis but not c-Jun phosphorylation. In neuroblastoma NO-induced Ser-63 phosphorylation of c-Jun and apoptosis were by JNK We that apoptosis is by Ser-63 phosphorylation of c-Jun of caspase-3 activation in neuroblastoma In NO NH2-terminal NH2-terminal in of and NO activation is that NO to NO can in of which and by in which to apoptosis However, that in in to NO not NO can activity of in of of transcriptional has been in of of apoptosis, which can on and of transcriptional by in of of c-Jun In phosphorylation of Ser-63 and Ser-73 in NH2-terminal of c-Jun, which is by c-Jun NH2-terminal kinases (JNKs) activity of c-Jun transcriptional c-Jun NH2-terminal phosphorylation on Ser-63 and Ser-73 can c-Jun phosphorylation is to required for of c-Jun of c-Jun phosphorylation in apoptosis is but c-Jun phosphorylation is in to and is in by c-Jun phosphorylation kinases and which by and JNK and been in with that NO apoptosis in cells c-Jun phosphorylation is for apoptosis of cells and is required for in that all JNK activity to apoptosis induced by of of apoptosis, which is in but in that c-Jun phosphorylation is but not in that in SH-Sy5y cells, activity of in of is required for of of NO-induced apoptosis. NO c-Jun phosphorylation and apoptosis that phosphorylation of c-Jun on Ser-63 NO-induced apoptosis of neuroblastoma A is which can for and of neuroblastoma and neuroblastoma SH-Sy5y and were of and c-Jun, and JNK were was and were and were was and were and were in were dominant-negative c-Jun was dominant-negative in c-Jun were by on and were were by of c-Jun and were by of and dominant-negative was by of and was by of and and SH-Sy5y and cells were in and that is to cells were in and were SH-Sy5y cells following stably cells were and in with and of of and of were SH-Sy5y cells in cells were with for was and cells were with were with of in and to of was to of and activity was in of was to activity for activity of and of were in cells in cells were with for and were and activity was by of and of was by in by cells were in and with for to was to and for of can to in was of of cells were and was with an of activity in and was was of by of activity of was with cells were in and and and was were with in in of and for was with of and of of were by to cells were in of and was to and of was for and to for of was on and and of was was in neuroblastoma and were of and was with and was of and c-Jun phosphorylation were JNK c-Jun on and in SH-Sy5y NO been to and by NO SH-Sy5y neuroblastoma cells to induced by NO in and of is apoptosis in was of to SH-Sy5y cells and with of JNK activity of kinases for c-Jun NH2-terminal phosphorylation Ser-63 and Ser-73 of c-Jun were of SH-Sy5y cells by and A and c-Jun phosphorylation on Ser-63 was of phosphorylation on Ser-73 was In of SH-Sy5y cells in of Ser-63 and Ser-73 phosphorylation JNK activation and phosphorylation of c-Jun on Ser-63 of NO apoptosis. Ser-63 phosphorylation and of SH-Sy5y cells and of induced Ser-63 phosphorylation of c-Jun not that c-Jun is of of in Ser-73 phosphorylation that with of that Ser-63 phosphorylation is an not in and but in c-Jun phosphorylation to NO-induced apoptosis, stably SH-Sy5y cells with dominant-negative of In Ser-63 was mutated to alanine and in Ser-73 was mutated to alanine In Ser-63 and Ser-73 were mutated to which of c-Jun to that JNK activity by JNK in an for in which not in of phosphorylation of c-Jun on Ser-63 in to was in of cells and Ser-73 phosphorylation of c-Jun in to was in cells with cells were in cells not In NO-induced phosphorylation of c-Jun on Ser-63 in that of c-Jun mutated to not JNK of not c-Jun phosphorylation in SH-Sy5y of c-Jun in with of of of and were with and cells were in were on and and to an of and were with and were in for an 73. of and were with for were in for an was in all of cells and cells to NO and of which were to apoptosis, of and cells to with cells Importantly, to to NO with cells In cells were to cells in to that Ser-63 phosphorylation of c-Jun is in NO-induced, but not of and of SH-Sy5y cells to and cells and cells were with for of cells was of in and cells and cells were with of cells was of in of c-Jun for and in to phosphorylation of Ser-63 and Ser-73 has been to to c-Jun-dependent and of serines of c-Jun to that NO c-Jun phosphorylation on and and cells to Ser-63 phosphorylation can potentiate c-Jun and that were to in SH-Sy5y cells NO However, and were in In with that NO-induced activation of to in SH-Sy5y and cells but was in cells c-Jun and that of Ser-63 (but not Ser-73) is required for NO-induced that and by by of c-Jun is required for and in to c-Jun in of c-Jun, were with with SH-Sy5y cells were with for and activity was and activity was an was with and cells were with for and activity was and activity was an to NO-induced and in was to for NO-induced apoptosis of SH-Sy5y cells of caspase-3 activity by caspase-3 that by and caspase-3 of NO-induced Ser-63 phosphorylation of c-Jun were to in of that of c-Jun phosphorylation. of were and has been We caspase-3 activity in and cells NO and that caspase-3 activity was inhibited in cells with cells, cells caspase-3 activity that caspase-3 to NO-induced apoptosis of SH-Sy5y cells, that c-Jun phosphorylation on Ser-63 (but not Ser-73) NO-induced apoptosis and that caspase-3 to apoptosis of c-Jun to NO-induced apoptosis of SH-Sy5y cells of c-Jun SH-Sy5y cells were with in of of caspase-3 inhibitor for and of cells was SH-Sy5y cells were with in of for and caspase-3 activity was In A and in SH-Sy5y cells were with in of for and were on and to an and cells and cells were with for and caspase-3 activity was by caspase-3 of in and NO-induced Ser-63 phosphorylation in SH-Sy5y of and cells and cells were to for to in were on and to an c-Jun was of c-Jun on Ser-63 and in that in c-Jun phosphorylation in to stably SH-Sy5y cells with of and cells phosphorylation of c-Jun on Ser-63 A and that for NO c-Jun phosphorylation in SH-Sy5y and to apoptosis of NO that was to that in cells A of caspase-3 of was in and cells that of JNK to of Ser-63 phosphorylation of c-Jun and of and NO-induced apoptosis and caspase-3 activation in SH-Sy5y cells and cells were to of NO for of cells was cells and cells were to for and caspase-3 activity was In A and of cells, in c-Jun on Ser-63 in NO-induced of was to c-Jun phosphorylation on Ser-63 in NO-induced apoptosis in neuroblastoma and to an to neuroblastoma cells Ser-63 phosphorylation of c-Jun Ser-73 phosphorylation was with SH-Sy5y cells, Ser-63 and Ser-73 phosphorylation of c-Jun in cells A which JNK activity Ser-63 phosphorylation and of cells In prevented Ser-63 phosphorylation of cells and that JNK of kinases c-Jun in NO-induced apoptosis and that c-Jun phosphorylation on Ser-63 an in of neuroblastoma JNK inhibitor c-Jun phosphorylation on Ser-63 and apoptosis in neuroblastoma cells were with for in were on and and to 63 73. cells with for Ser-63 and Ser-73 phosphorylation. c-Jun phosphorylation is of JNK cells were with of JNK for c-Jun phosphorylation on Ser-63 was in cells were with of for and of was in that of NO to activation of kinases and activation of in induced apoptosis of cells which in of to that NO can in and that can modulate apoptosis induced by However, of NO-induced and in apoptosis has not been In is and Ser-63 and Ser-73 and is that transcriptional activation of c-Jun in and on phosphorylation of that Ser-63 (but not Ser-73) phosphorylation of c-Jun NO-induced apoptosis of neuroblastoma of NO induced activation of and of induced phosphorylation of c-Jun on Ser-63 to and of apoptosis. and cells (but not to apoptosis by NO by and caspase-3 Moreover, and cells to NO with Ser-63 phosphorylation and caspase-3 that for phosphorylating c-Jun on which is by that inhibitor to Ser-63 phosphorylation of in Ser-63 phosphorylation and NO-induced apoptosis of neuroblastoma of and c-Jun and to is that phosphorylation of is in However, that JNK activity is in and cells, that JNK c-Jun in which NO that Ser-63 of c-Jun is in is not NO Ser-63 but is of and NO that Ser-63. NO Ser-73 of c-Jun Ser-73 is by which Ser-63 phosphorylation of c-Jun to caspase-3 activation and Ser-63 phosphorylation c-Jun, which is by of and which that that c-Jun is of an by in with that c-Jun is in NO Ser-63 phosphorylation of with c-Jun, in to is that to in apoptosis and which but and is Ser-63 phosphorylation to apoptosis transcriptional by of c-Jun that that SH-Sy5y cells in which of c-Jun is to NO-induced apoptosis. is in to and in all of which neuroblastoma cells to apoptosis. is to of dominant-negative c-Jun and neuroblastoma cells in an to of in NO-induced apoptosis. A is in which can for dominant-negative is to cells to NO in of an by of of not Ser-63 phosphorylation of c-Jun in of NO which in is to for of c-Jun in which c-Jun is by and which is in to of In can by and of of dominant-negative of c-Jun and on of SH-Sy5y cells to in SH-Sy5y cells to of of phosphorylation of c-Jun on Ser-63 and cells to apoptosis. and caspase-3 is in and cells to apoptosis SH-Sy5y activity of to to c-Jun, which has and to cells that is in and in and and is in cells In and of cells to apoptosis with SH-Sy5y cells and cells with and was that c-Jun can cells apoptosis of c-Jun but in cells JNK can apoptosis, and c-Jun However, NO was not of apoptosis with report that can in neuroblastoma which to in following A activity of of c-Jun phosphorylation on is to of of In of NO to c-Jun phosphorylation on Ser-63 by JNK that apoptosis c-Jun In NO NH2-terminal NH2-terminal in of and NO activation is that NO to NO can in of which and by in which to apoptosis However, that in in to NO not NO can activity of in of nitric oxide dominant-negative c-Jun NH2-terminal dominant-negative c-Jun nitric oxide dominant-negative c-Jun NH2-terminal dominant-negative c-Jun c-Jun, of transcriptional has been in of of apoptosis, which can on and of transcriptional by in of of c-Jun In phosphorylation of Ser-63 and Ser-73 in NH2-terminal of c-Jun, which is by c-Jun NH2-terminal kinases (JNKs) activity of c-Jun transcriptional c-Jun NH2-terminal phosphorylation on Ser-63 and Ser-73 can c-Jun phosphorylation is to required for of c-Jun of c-Jun phosphorylation in apoptosis is but c-Jun phosphorylation is in to and is in by c-Jun phosphorylation kinases and which by and JNK and been in with that NO apoptosis in cells c-Jun phosphorylation is for apoptosis of cells and is required for in that all JNK activity to apoptosis induced by of of apoptosis, which is in but in that c-Jun phosphorylation is but not in We that in SH-Sy5y cells, activity of in of is required for of of NO-induced apoptosis. NO c-Jun phosphorylation and apoptosis that phosphorylation of c-Jun on Ser-63 NO-induced apoptosis of neuroblastoma A is which can for and of neuroblastoma and neuroblastoma SH-Sy5y and were of and c-Jun, and JNK were was and were and were was and were and were in were dominant-negative c-Jun was dominant-negative in c-Jun were by on and were were by of c-Jun and were by of and dominant-negative was by of and was by of and and SH-Sy5y and cells were in and that is to cells were in and were SH-Sy5y cells following stably cells were and in with and of of and of were SH-Sy5y cells in cells were with for was and cells were with were with of in and to of was to of and activity was in of was to activity for activity of and of were in cells in cells were with for and were and activity was by of and of was by in by cells were in and with for to was to and for of can to in was of of cells were and was with an of activity in and was was of by of activity of was with cells were in and and and was were with in in of and for was with of and of of were by to cells were in of and was to and of was for and to for of was on and and of was was in neuroblastoma and were of and was with and was of and c-Jun phosphorylation were and neuroblastoma SH-Sy5y and were of and c-Jun, and JNK were was and were and were was and were and were in were dominant-negative c-Jun was dominant-negative in c-Jun were by on and were were by of c-Jun and were by of and dominant-negative was by of and was by of and and SH-Sy5y and cells were in and that is to cells were in and were SH-Sy5y cells following stably cells were and in with and of of and of were SH-Sy5y cells in cells were with for was and cells were with were with of in and to of was to of and activity was in of was to activity for activity of and of were in cells in cells were with for and were and activity was by of and of was by in by cells were in and with for to was to and for of can to in was of of cells were and was with an of activity in and was was of by of activity of was with cells were in and and and was were with in in of and for was with of and of of were by to cells were in of and was to and of was for and to for of was on and and of was was in neuroblastoma and were of and was with and was of and c-Jun phosphorylation were JNK c-Jun on and in SH-Sy5y NO been to and by NO SH-Sy5y neuroblastoma cells to induced by NO in and of is apoptosis in was of to SH-Sy5y cells and with of JNK activity of kinases for c-Jun NH2-terminal phosphorylation Ser-63 and Ser-73 of c-Jun were of SH-Sy5y cells by and A and c-Jun phosphorylation on Ser-63 was of phosphorylation on Ser-73 was In of SH-Sy5y cells in of Ser-63 and Ser-73 phosphorylation JNK activation and phosphorylation of c-Jun on Ser-63 of NO apoptosis. Ser-63 phosphorylation and of SH-Sy5y cells and of induced Ser-63 phosphorylation of c-Jun not that c-Jun is of of in Ser-73 phosphorylation that with of that Ser-63 phosphorylation is an not in and but in c-Jun phosphorylation to NO-induced apoptosis, stably SH-Sy5y cells with dominant-negative of In Ser-63 was mutated to alanine and in Ser-73 was mutated to alanine In Ser-63 and Ser-73 were mutated to which of c-Jun to that JNK activity by JNK in an for in which not in of phosphorylation of c-Jun on Ser-63 in to was in of cells and Ser-73 phosphorylation of c-Jun in to was in cells with cells were in cells not In NO-induced phosphorylation of c-Jun on Ser-63 in that of c-Jun mutated to not JNK of cells and cells to NO and of which were to apoptosis, of and cells to with cells Importantly, to to NO with cells In cells were to cells in to that Ser-63 phosphorylation of c-Jun is in NO-induced, but not of and of SH-Sy5y cells to and cells and cells were with for of cells was of in and cells and cells were with of cells was of in of c-Jun for and in to phosphorylation of Ser-63 and Ser-73 has been to to c-Jun-dependent and of serines of c-Jun to that NO c-Jun phosphorylation on and and cells to Ser-63 phosphorylation can potentiate c-Jun and that were to in SH-Sy5y cells NO However, and were in In with that NO-induced activation of to in SH-Sy5y and cells but was in cells c-Jun and that of Ser-63 (but not Ser-73) is required for NO-induced that and by by of c-Jun is required for and in to c-Jun in of c-Jun, were with with SH-Sy5y cells were with for and activity was and activity was an was with and cells were with for and activity was and activity was an to NO-induced and in was to for NO-induced apoptosis of SH-Sy5y cells of caspase-3 activity by caspase-3 that by and caspase-3 of NO-induced Ser-63 phosphorylation of c-Jun were to in of that of c-Jun phosphorylation. of were and has been We caspase-3 activity in and cells NO and that caspase-3 activity was inhibited in cells with cells, cells caspase-3 activity that caspase-3 to NO-induced apoptosis of SH-Sy5y cells, that c-Jun phosphorylation on Ser-63 (but not Ser-73) NO-induced apoptosis and that caspase-3 to apoptosis of c-Jun to NO-induced apoptosis of SH-Sy5y cells of c-Jun SH-Sy5y cells were with in of of caspase-3 inhibitor for and of cells was SH-Sy5y cells were with in of for and caspase-3 activity was In A and in SH-Sy5y cells were with in of for and were on and to an and cells and cells were with for and caspase-3 activity was by caspase-3 of in and NO-induced Ser-63 phosphorylation in SH-Sy5y of and cells and cells were to for to in were on and to an c-Jun was of c-Jun on Ser-63 and in that in c-Jun phosphorylation in to stably SH-Sy5y cells with of and cells phosphorylation of c-Jun on Ser-63 A and that for NO c-Jun phosphorylation in SH-Sy5y and to apoptosis of NO that was to that in cells A of caspase-3 of was in and cells that of JNK to of Ser-63 phosphorylation of c-Jun and of and NO-induced apoptosis and caspase-3 activation in SH-Sy5y cells and cells were to of NO for of cells was cells and cells were to for and caspase-3 activity was In A and of cells, in c-Jun on Ser-63 in NO-induced of was to c-Jun phosphorylation on Ser-63 in NO-induced apoptosis in neuroblastoma and to an to neuroblastoma cells Ser-63 phosphorylation of c-Jun Ser-73 phosphorylation was with SH-Sy5y cells, Ser-63 and Ser-73 phosphorylation of c-Jun in cells A which JNK activity Ser-63 phosphorylation and of cells In prevented Ser-63 phosphorylation of cells and that JNK of kinases c-Jun in NO-induced apoptosis and that c-Jun phosphorylation on Ser-63 an in of neuroblastoma JNK inhibitor c-Jun phosphorylation on Ser-63 and apoptosis in neuroblastoma cells were with for in were on and and to 63 73. cells with for Ser-63 and Ser-73 phosphorylation. c-Jun phosphorylation is of JNK cells were with of JNK for c-Jun phosphorylation on Ser-63 was in cells were with of for and of was in NO JNK c-Jun on and in SH-Sy5y NO been to and by NO SH-Sy5y neuroblastoma cells to induced by NO in and of is apoptosis in was of to SH-Sy5y cells and with of JNK activity of kinases for c-Jun NH2-terminal phosphorylation Ser-63 and Ser-73 of c-Jun were of SH-Sy5y cells by and A and c-Jun phosphorylation on Ser-63 was of phosphorylation on Ser-73 was In of SH-Sy5y cells in of Ser-63 and Ser-73 phosphorylation JNK activation and phosphorylation of c-Jun on Ser-63 of NO apoptosis. Ser-63 phosphorylation and of SH-Sy5y cells and of induced Ser-63 phosphorylation of c-Jun not that c-Jun is of of in Ser-73 phosphorylation that with of that Ser-63 phosphorylation is an not NO-induced in and but in c-Jun phosphorylation to NO-induced apoptosis, stably SH-Sy5y cells with dominant-negative of In Ser-63 was mutated to alanine and in Ser-73 was mutated to alanine In Ser-63 and Ser-73 were mutated to which of c-Jun to that JNK activity by JNK in an for in which not in of phosphorylation of c-Jun on Ser-63 in to was in of cells and Ser-73 phosphorylation of c-Jun in to was in cells with cells were in cells not In NO-induced phosphorylation of c-Jun on Ser-63 in that of c-Jun mutated to not JNK activity. We of cells and cells to NO and of which were to apoptosis, of and cells to with cells Importantly, to to NO with cells In cells were to cells in to that Ser-63 phosphorylation of c-Jun is in NO-induced, but not Ser-63 of c-Jun for and in to phosphorylation of Ser-63 and Ser-73 has been to to c-Jun-dependent and of serines of c-Jun to that NO c-Jun phosphorylation on and and cells to Ser-63 phosphorylation can potentiate c-Jun and that were to in SH-Sy5y cells NO However, and were in In with that NO-induced activation of to in SH-Sy5y and cells but was in cells c-Jun and that of Ser-63 (but not Ser-73) is required for NO-induced that and by by to NO-induced and in was to for NO-induced apoptosis of SH-Sy5y cells of caspase-3 activity by caspase-3 that by and caspase-3 of NO-induced Ser-63 phosphorylation of c-Jun were to in of that of c-Jun phosphorylation. of were and has been We caspase-3 activity in and cells NO and that caspase-3 activity was inhibited in cells with cells, cells caspase-3 activity that caspase-3 to NO-induced apoptosis of SH-Sy5y cells, that c-Jun phosphorylation on Ser-63 (but not Ser-73) NO-induced apoptosis and that caspase-3 to apoptosis of c-Jun phosphorylation. of c-Jun on Ser-63 and in that in c-Jun phosphorylation in to stably SH-Sy5y cells with of and cells phosphorylation of c-Jun on Ser-63 A and that for NO c-Jun phosphorylation in SH-Sy5y and to apoptosis of NO that was to that in cells A of caspase-3 of was in and cells that of JNK to of Ser-63 phosphorylation of c-Jun and of c-Jun on Ser-63 in NO-induced of was to c-Jun phosphorylation on Ser-63 in NO-induced apoptosis in neuroblastoma and to an to neuroblastoma cells Ser-63 phosphorylation of c-Jun Ser-73 phosphorylation was with SH-Sy5y cells, Ser-63 and Ser-73 phosphorylation of c-Jun in cells A which JNK activity Ser-63 phosphorylation and of cells In prevented Ser-63 phosphorylation of cells and that JNK of kinases c-Jun in NO-induced apoptosis and that c-Jun phosphorylation on Ser-63 an in of neuroblastoma that of NO to activation of kinases and activation of in induced apoptosis of cells which in of to that NO can in and that can modulate apoptosis induced by However, of NO-induced and in apoptosis has not been In is and Ser-63 and Ser-73 and is that transcriptional activation of c-Jun in and on phosphorylation of that Ser-63 (but not Ser-73) phosphorylation of c-Jun NO-induced apoptosis of neuroblastoma of NO induced activation of and of induced phosphorylation of c-Jun on Ser-63 to and of apoptosis. and cells (but not to apoptosis by NO by and caspase-3 Moreover, and cells to NO with Ser-63 phosphorylation and caspase-3 that for phosphorylating c-Jun on which is by that inhibitor to Ser-63 phosphorylation of in Ser-63 phosphorylation and NO-induced apoptosis of neuroblastoma of and c-Jun and to is that phosphorylation of is in However, that JNK activity is in and cells, that JNK c-Jun in which NO that Ser-63 of c-Jun is in is not NO Ser-63 but is of and NO that Ser-63. NO Ser-73 of c-Jun Ser-73 is by which Ser-63 phosphorylation of c-Jun to caspase-3 activation and Ser-63 phosphorylation c-Jun, which is by of and which that that c-Jun is of an by in with that c-Jun is in NO Ser-63 phosphorylation of with c-Jun, in to is that to in apoptosis and which but and is Ser-63 phosphorylation to apoptosis transcriptional by of c-Jun that that SH-Sy5y cells in which of c-Jun is to NO-induced apoptosis. is in to and in all of which neuroblastoma cells to apoptosis. is to of dominant-negative c-Jun and neuroblastoma cells in an to of in NO-induced apoptosis. A is in which can for dominant-negative is to cells to NO in of an by of of not Ser-63 phosphorylation of c-Jun in of NO which in is to for of c-Jun in which c-Jun is by and which is in to of In can by and of to cells that is in and in and and is in cells In and of cells to apoptosis with SH-Sy5y cells and cells with and was that c-Jun can cells apoptosis of c-Jun but in cells JNK can apoptosis, and c-Jun However, NO was not of apoptosis with report that can in neuroblastoma which to in following A activity of of c-Jun phosphorylation on is to of of In of NO to c-Jun phosphorylation on Ser-63 by JNK that apoptosis c-Jun that of NO to activation of kinases and activation of in induced apoptosis of cells which in of to that NO can in and that can modulate apoptosis induced by However, of NO-induced and in apoptosis has not been In is and Ser-63 and Ser-73 and is that transcriptional activation of c-Jun in and on phosphorylation of that Ser-63 (but not Ser-73) phosphorylation of c-Jun NO-induced apoptosis of neuroblastoma of NO induced activation of and of induced phosphorylation of c-Jun on Ser-63 to and of apoptosis. and cells (but not to apoptosis by NO by and caspase-3 Moreover, and cells to NO with Ser-63 phosphorylation and caspase-3 that for phosphorylating c-Jun on which is by that inhibitor to Ser-63 phosphorylation of in Ser-63 phosphorylation and NO-induced apoptosis of neuroblastoma of and c-Jun and to is that phosphorylation of is in However, that JNK activity is in and cells, that JNK c-Jun in which NO that Ser-63 of c-Jun is in is not NO Ser-63 but is of and NO that Ser-63. NO Ser-73 of c-Jun Ser-73 phosphorylation. is by which Ser-63 phosphorylation of c-Jun to caspase-3 activation and Ser-63 phosphorylation c-Jun, which is by of and which that that c-Jun is of an by in with that c-Jun is in NO Ser-63 phosphorylation of with c-Jun, in to is that to in apoptosis and which but and is Ser-63 phosphorylation to apoptosis transcriptional by of c-Jun that In that SH-Sy5y cells in which of c-Jun is to NO-induced apoptosis. is in to and in all of which neuroblastoma cells to apoptosis. is to of dominant-negative c-Jun and neuroblastoma cells in an to of in NO-induced apoptosis. A is in which can for dominant-negative is to cells to NO in of an by of of not Ser-63 phosphorylation of c-Jun in of NO which in is to for of c-Jun in which c-Jun is by and which is in to of In can by and of In to cells that is in and in and and is in cells In and of cells to apoptosis with SH-Sy5y cells and cells with and was that c-Jun can cells apoptosis of c-Jun but in cells JNK can apoptosis, and c-Jun However, NO was not of apoptosis with report that can in neuroblastoma which to in following A activity of of c-Jun phosphorylation on is to of of In of NO to c-Jun phosphorylation on Ser-63 by JNK that apoptosis c-Jun We of for SH-Sy5y cells and for We to for of for and of for We and for and for with