Forced Expression of Survivin-2B Abrogates Mitotic Cells and Induces Mitochondria-dependent Apoptosis by Blockade of Tubulin Polymerization and Modulation of Bcl-2, Bax, and Survivin

It has been previously shown that both survivin and the survivin splice variant survivin-2B are localized in mitochondria. Whereas the mechanism involved in blockade of mitochondria-mediated apoptosis by survivin has been extensively studied, the role of survivin-2B in regulation of apoptosis has not been well defined. In the present study, we report that in addition to mitochondria, survivin-2B is also localized in the microtubule organization center (MTOC) and, in contrast to other survivin isoforms (i.e. survivin and survivin-ΔEx3), behaves as a proapoptotic molecule. We show that forced expression of survivin-2B blocks tubulin polymerization, ablates and mitochondria-mediated apoptosis by survivin-2B by mitochondria, of and and of of the mechanism the of apoptosis by forced expression of survivin-2B of the and of the in mitochondria, the that of not survivin also survivin-2B and that forced expression of survivin-2B to and of survivin-2B by to survivin-2B and to It has been previously shown that both survivin and the survivin splice variant survivin-2B are localized in mitochondria. Whereas the mechanism involved in blockade of mitochondria-mediated apoptosis by survivin has been extensively studied, the role of survivin-2B in regulation of apoptosis has not been well defined. In the present study, we report that in addition to mitochondria, survivin-2B is also localized in the microtubule organization center (MTOC) and, in contrast to other survivin isoforms (i.e. survivin and survivin-ΔEx3), behaves as a proapoptotic molecule. We show that forced expression of survivin-2B blocks tubulin polymerization, ablates and mitochondria-mediated apoptosis by survivin-2B by mitochondria, of and and of of the mechanism the of apoptosis by forced expression of survivin-2B of the and of the in mitochondria, the that of not survivin also survivin-2B and that forced expression of survivin-2B to and of survivin-2B by to survivin-2B and to is in is in and is involved in both of apoptosis and regulation of survivin a role in the and mitochondria-mediated apoptosis survivin is and to the to a and by the the survivin and that is a of is the of of mitochondria-mediated apoptosis by Whereas the of survivin has been extensively the role of splice variant survivin-2B in apoptosis has not been well that the expression of survivin-2B is in expression in is In survivin and splice variant show survivin-2B expression is in a role of survivin-2B in in a in survivin-2B expression in in the expression of survivin and In both survivin and survivin-2B is expression is in in of the and, in expression of survivin-2B is the of and that survivin-2B role in to survivin survivin-2B to the mechanism by survivin-2B in of apoptosis has not been well study, we report that survivin-2B also to the microtubule organization center organization of organization of expression of survivin-2B blocks tubulin and the expression of the and the the expression of in mitochondria. We that survivin-2B a and of regulation and mechanism and and as previously and and and and and the of of the of survivin-2B by a of and the and survivin-2B expression by the survivin-2B the and the the and in of the survivin-2B the the the survivin-2B by and and the the to the survivin-2B as the and in in the of as survivin-2B by of the by a of of and of to expression in of expression in the and of and of in of and of in apoptosis of and of in and of and of in in of and in and as previously that in the survivin-2B a by and in and as to and and in of and of the the in of and of of by and to the of survivin-2B In as a are to the to of by to a of in and in a by well of a in well are as a are the and and the expression the and by as previously by the in to and a by and shown as a of in in in of and in and and in and in by a of in in and as In and a and survivin-2B and by and of to a of in the and also as a in and not present in by the to of well in to a of the of by of of of of to the to as of and of well in and and of and the survivin-2B expression by the as by the and to survivin-2B and to the of a of and and by of and and the a a a of and the as and as previously and survivin-2B expression by of of the the by the by and in and as the and and and and the as the the and of in of well of the well and a a and of to to by of and to and the a of the the In the in the and by in the and the the a a of as and to as of of in the of a and the of and by the of the of and the of of the role of survivin-2B in we expression of that expression of in in the by the of the of we by and that survivin-2B expression the of that survivin-2B a role in and the mechanism of we to survivin-2B is to We that the microtubule organization center expression in the is the in the we the survivin-2B and We and the in also and expression that the the of both and the of survivin-2B not the expression and and is as is by and to the the as blocks tubulin expression and by of the and and as of a role in of survivin-2B in the and to the that survivin-2B a role in the regulation of we the to tubulin in the by in in the by by shown in of tubulin the in the not in the a of tubulin in by of In tubulin not in the of and has been that survivin-2B expression is in the of the of survivin-2B and of survivin-2B the by in both and and that forced expression of survivin-2B in and and and and and and and and we by expression of the also the the that in survivin-2B survivin-2B that of survivin-2B in to expression of and expression as expression of the survivin-2B by and by by are the are the as in and the of are expression the and as shown and by and by the in are the in expression of survivin-2B of survivin-2B by a previously and and as by are the of survivin-2B by to of survivin-2B and by as by to are the a we shown that survivin-2B is localized in to that survivin-2B the forced expression of not and and and that apoptosis by survivin-2B a a a of and in in and to a in expression of and of and is the forced expression of forced expression of not a the and are the of and the expression of and of by and not and of by and not of to are in and is expression is as in of and in a in and previously shown that of survivin expression is and that of of survivin expression to survivin-2B mechanism survivin we that forced expression of survivin-2B in forced expression of survivin-2B by in and and and both and and and and in in and the In as we show in of survivin-2B to are also the role of survivin-2B in the of and expression of survivin-2B to survivin and survivin-2B expression by the expression of to and and the the are the and and to is the and in and are expression of survivin-2B to of survivin-2B shown in and and expression as by to are the and expression in mitochondria. and and and and and and and as of and by as as in and of the of and expression forced expression of and the expression of and by a expression of a as and of in of and of in the mechanism by survivin-2B of the we forced expression of survivin-2B in is to the expression of We that forced expression of survivin-2B both and and in and and the expression of survivin-2B expression that of is a a of we to expression in and that forced expression of not the expression of in mitochondria, also the of in we the of a of expression forced expression of survivin-2B is that of the to is the of and that is a of survivin we the expression of survivin and in forced expression of expression of survivin expression in (i.e. of by In forced expression of survivin-2B the expression of in the of to apoptosis forced expression of a mechanism the mechanism survivin-2B of and to of has been to the of survivin is the and of the survivin splice variant In we to the role of survivin-2B in regulation and apoptosis We the in addition to localized to survivin-2B and in and and blocks tubulin a the that forced expression of survivin-2B is a of to of we a of the of In we to that we a of survivin-2B that and in the we not a of tubulin the in and of microtubule in that the survivin-2B is contrast to a role of survivin in microtubule and has a the of of survivin-2B that the of survivin-2B to the in the of survivin-2B in the is in In in survivin-2B is localized in the has been shown that a of survivin is in of and not in as We also that is survivin-2B present in in in In that survivin-2B is localized to the of and and is the that the of survivin-2B to is that the of survivin-2B the in to a of survivin-2B in and shown in forced expression of survivin-2B not in in and and is that the regulation of the survivin to in survivin in not in in that forced expression of survivin-2B in to the of the and of the in mitochondria. the the in expression by survivin-2B to is that is blockade of mitochondria-mediated expression of in mitochondria-mediated apoptosis the other of the to is also to a of mitochondria-mediated In in the is a and to the in expression forced expression of survivin-2B of the to mitochondria. of the involved in of and of in mitochondria, are and a mechanism of (i.e. mitochondria, of and and of previously that is a of survivin in not in as and that is the of mitochondria-mediated in to survivin is the and apoptosis mechanism mitochondria-mediated apoptosis blockade of survivin the by the the in the of survivin of and by of survivin-2B and of the of survivin-2B survivin the of survivin forced expression of survivin-2B is also the of survivin in forced expression of survivin-2B blockade of survivin the the of survivin and of the we that are to and to of survivin in to we to that the survivin both survivin and other survivin splice to the of survivin-2B survivin in as we the and in also in we to the of not in the also in the of a role in In the the microtubule by a of a a not to the also of the in the is that the is a of both we to the of the expression of survivin is apoptosis in survivin-2B expression is that survivin-2B and survivin has been that of the apoptosis by the is of survivin and In both survivin and the in that both of survivin and of that survivin and survivin-2B of survivin-2B and of survivin a a mechanism by survivin-2B as a proapoptotic molecule. expression of survivin-2B and the by blockade of tubulin and of and survivin is in is in and is involved in both of apoptosis and regulation of survivin a role in the and mitochondria-mediated apoptosis survivin is and to the to a and by the the survivin and that is a of is the of of mitochondria-mediated apoptosis by Whereas the of survivin has been extensively the role of splice variant survivin-2B in apoptosis has not been well that the expression of survivin-2B is in expression in is In survivin and splice variant show survivin-2B expression is in a role of survivin-2B in in a in survivin-2B expression in in the expression of survivin and In both survivin and survivin-2B is expression is in in of the and, in expression of survivin-2B is the of and that survivin-2B role in to survivin survivin-2B to the mechanism by survivin-2B in of apoptosis has not been well defined. In study, we report that survivin-2B also to the microtubule organization center organization of organization of expression of survivin-2B blocks tubulin and the expression of the and the the expression of in mitochondria. We that survivin-2B a and of regulation and mechanism microtubule organization center of apoptosis microtubule organization center of apoptosis and and as previously and and and and and the of of the of survivin-2B by a of and the and survivin-2B expression by the survivin-2B the and the the and in of the survivin-2B the the the survivin-2B by and and the the to the survivin-2B as the and in in the of as survivin-2B by of the by a of of and of to expression in of expression in the and of and of in of and of in apoptosis of and of in and of and of in in of and in and as previously that in the survivin-2B a by and in and as to and and in of and of the the in of and of of by and to the of survivin-2B In as a are to the to of by to a of in and in a by well of a in well are as a are the and and the expression the and by as previously by the in to and a by and shown as a of in in in of and in and and in and in by a of in in and as In and a and survivin-2B and by and of to a of in the and also as a in and not present in by the to of well in to a of the of by of of of of to the to as of and of well in and and of and the survivin-2B expression by the as by the and to survivin-2B and to the of a of and and by of and and the a a a of and the as and as previously and survivin-2B expression by of of the the by the by and in and as the and and and and the as the the and of in of well of the well and a a and of to to by of and to and the a of the the In the in the and by in the and the the a a of as and to as of of in the of a and the of and by the of the of and the of and and as previously and and and and and the of of the of survivin-2B by a of and the and survivin-2B expression by the survivin-2B the and the the and in of the survivin-2B the the the survivin-2B by and and the the to the survivin-2B as the and in in the of as survivin-2B by of the by a of of and of to expression in of expression in the and of and of in of and of in apoptosis of and of in and of and of in in of and in and as previously that in the survivin-2B a by and in and as to and and in of and of the the in of and of of by and to the of survivin-2B In as a are to the to of by to a of in and in a by well of a in well are as a are the and and the expression the and by as previously by the in to and a by and shown as a of in in in of and in and and in and in by a of in in and as In and a and survivin-2B and by and of to a of in the and also as a in and not present in by the to of well in to a of the of by of of of of to the to as of and of well in and and of and the survivin-2B expression by the as by the and to survivin-2B and to the of a of and and by of and and the a a a of and the as and as previously and survivin-2B expression by of of the the by the by and in and as the and and and and the as the the and of in of well of the well and a a and of to to by of and to and the a of the the In the in the and by in the and the the a a of as and to as of of in the of a and the of and by the of the of and the of of the role of survivin-2B in we expression of that expression of in in the by the of the of we by and that survivin-2B expression the of that survivin-2B a role in and the mechanism of we to survivin-2B is to We that the microtubule organization center expression in the is the in the we the survivin-2B and We and the in also and expression that the the of both and the of survivin-2B not the blocks tubulin expression and by of the and and as of a role in of survivin-2B in the and to the that survivin-2B a role in the regulation of we the to tubulin in the by in in the by by shown in of tubulin the in the not in the a of tubulin in by of In tubulin not in the of and has been that survivin-2B expression is in the of the of survivin-2B and of survivin-2B the by in both and and that forced expression of survivin-2B in and and and and and and and and we by expression of the also the the that in survivin-2B survivin-2B that of survivin-2B in to expression of and expression as expression of the survivin-2B by and by by are the are the as in and the of are expression the and as shown and by and by the in are the in expression of survivin-2B of survivin-2B by a previously and and as by are the of survivin-2B by to of survivin-2B and by as by to are the a we shown that survivin-2B is localized in to that survivin-2B the forced expression of not and and and that apoptosis by survivin-2B a a a of and in in and to a in expression of and of and is the forced expression of forced expression of not a the and are the of and the expression of and of by and not and of by and not of to are in and is expression is as in of and in a in and previously shown that of survivin expression is and that of of survivin expression to survivin-2B mechanism survivin we that forced expression of survivin-2B in forced expression of survivin-2B by in and and and both and and and and in in and the In as we show in of survivin-2B to are also the role of survivin-2B in the of and expression of survivin-2B to survivin and survivin-2B expression by the expression of to and and the the are the and and to is the and in and are expression of survivin-2B to of survivin-2B shown in and and expression as by to are the and expression in mitochondria. and and and and and and and as of and by as as in and of the of and expression forced expression of and the expression of and by a expression of a as and of in of and of in the mechanism by survivin-2B of the we forced expression of survivin-2B in is to the expression of We that forced expression of survivin-2B both and and in and and the expression of survivin-2B expression that of is a a of we to expression in and that forced expression of not the expression of in mitochondria, also the of in we the of a of expression forced expression of survivin-2B is that of the to is the of and that is a of survivin we the expression of survivin and in forced expression of expression of survivin expression in (i.e. of by In forced expression of survivin-2B the expression of in the of to apoptosis forced expression of a mechanism the mechanism survivin-2B of and to of the role of survivin-2B in we expression of that expression of in in the by the of the of we by and that survivin-2B expression the of that survivin-2B a role in and the mechanism of we to survivin-2B is to We that the microtubule organization center expression in the is the in the we the survivin-2B and We and the in also and expression that the the of both and the of survivin-2B not the of a role in of survivin-2B in the and to the that survivin-2B a role in the regulation of we the to tubulin in the by in in the by by shown in of tubulin the in the not in the a of tubulin in by of In tubulin not in the of and has been that survivin-2B expression is in the of the of survivin-2B and of survivin-2B the by in both and and that forced expression of survivin-2B in and and and and and and and and we by expression of the also the the that in survivin-2B survivin-2B that of survivin-2B in to a we shown that survivin-2B is localized in to that survivin-2B the forced expression of not and and and that apoptosis by survivin-2B a a a of and in in and to a in of and in a in and previously shown that of survivin expression is and that of of survivin expression to survivin-2B mechanism survivin we that forced expression of survivin-2B in forced expression of survivin-2B by in and and and both and and and and in in and the In as we show in of survivin-2B to are also the role of survivin-2B in the of and of in of and of in the mechanism by survivin-2B of the we forced expression of survivin-2B in is to the expression of We that forced expression of survivin-2B both and and in and and the expression of survivin-2B expression that of is a a of we to expression in and that forced expression of not the expression of in mitochondria, also the of in we the of a of expression forced expression of survivin-2B It is that of the to is the of and that is a of survivin we the expression of survivin and in forced expression of expression of survivin expression in (i.e. of by In forced expression of survivin-2B the expression of in the of to apoptosis forced expression of a mechanism the mechanism survivin-2B of and to of has been to the of survivin is the and of the survivin splice variant In we to the role of survivin-2B in regulation and apoptosis We the in addition to localized to survivin-2B and in and and blocks tubulin a the that forced expression of survivin-2B is a of to of we a of the of In we to that we a of survivin-2B that and in the we not a of tubulin the in and of microtubule in that the survivin-2B is contrast to a role of survivin in microtubule and has a the of of survivin-2B that the of survivin-2B to the in the of survivin-2B in the is in In in survivin-2B is localized in the has been shown that a of survivin is in of and not in as We also that is survivin-2B present in in in In that survivin-2B is localized to the of and and is the that the of survivin-2B to is that the of survivin-2B the in to a of survivin-2B in and shown in forced expression of survivin-2B not in in and and is that the regulation of the survivin to in survivin in not in in that forced expression of survivin-2B in to the of the and of the in mitochondria. the the in expression by survivin-2B to is that is blockade of mitochondria-mediated expression of in mitochondria-mediated apoptosis the other of the to is also to a of mitochondria-mediated In in the is a and to the in expression forced expression of survivin-2B of the to mitochondria. of the involved in of and of in mitochondria, are and a mechanism of (i.e. mitochondria, of and and of previously that is a of survivin in not in as and that is the of mitochondria-mediated in to survivin is the and apoptosis mechanism mitochondria-mediated apoptosis blockade of survivin the by the the in the of survivin of and by of survivin-2B and of the of survivin-2B survivin the of survivin forced expression of survivin-2B is also the of survivin in forced expression of survivin-2B blockade of survivin the the of survivin and of the we that are to and to of survivin in to we to that the survivin both survivin and other survivin splice to the of survivin-2B survivin in as we the and in also in we to the of not in the also in the of a role in In the the microtubule by a of a a not to the also of the in the is that the is a of both we to the of the expression of survivin is apoptosis in survivin-2B expression is that survivin-2B and survivin has been that of the apoptosis by the is of survivin and In both survivin and the in that both of survivin and of that survivin and survivin-2B of survivin-2B and of survivin a a mechanism by survivin-2B as a proapoptotic molecule. expression of survivin-2B and the by blockade of tubulin and of and survivin of has been to the of survivin is the and of the survivin splice variant In we to the role of survivin-2B in regulation and apoptosis We the in addition to localized to survivin-2B and in and and blocks tubulin a the that forced expression of survivin-2B is a of to of we a of the of In we to that we a of survivin-2B that and in the we not a of tubulin the in and of microtubule in that the survivin-2B is contrast to a role of survivin in microtubule and has a the of of survivin-2B that the of survivin-2B to the in the of survivin-2B in the is in In in survivin-2B is localized in the has been shown that a of survivin is in of and not in as We also that is survivin-2B present in in in In that survivin-2B is localized to the of and and is the that the of survivin-2B to is that the of survivin-2B the in to a of survivin-2B in and shown in forced expression of survivin-2B not in in and and is that the regulation of the survivin to in survivin in not in We in that forced expression of survivin-2B in to the of the and of the in mitochondria. the the in expression by survivin-2B to is that is blockade of mitochondria-mediated expression of in mitochondria-mediated apoptosis the other of the to is also to a of mitochondria-mediated In in the is a and to the in expression forced expression of survivin-2B of the to mitochondria. of the involved in of and of in mitochondria, are and a mechanism of (i.e. mitochondria, of and and of previously that is a of survivin in not in as and that is the of mitochondria-mediated in to survivin is the and apoptosis mechanism mitochondria-mediated apoptosis blockade of survivin the by the the in the of survivin of and by of survivin-2B and of the of survivin-2B survivin the of survivin forced expression of survivin-2B is also the of survivin in forced expression of survivin-2B blockade of survivin the the of survivin and of the we that are to and to of survivin in to we to that the survivin both survivin and other survivin splice to the of survivin-2B survivin in as we the and in also in we to the of not in the also in the of a role in In the the microtubule by a of a a not to the also of the in the is that the is a of both we to the of the expression of survivin is apoptosis in survivin-2B expression is that survivin-2B and survivin has been that of the apoptosis by the is of survivin and In both survivin and the in that both of survivin and of that survivin and survivin-2B of survivin-2B and of survivin a In a mechanism by survivin-2B as a proapoptotic molecule. expression of survivin-2B and the by blockade of tubulin and of and survivin We the and and

Перевод пока недоступен