Physical and Functional Interactions between PML and MDM2

Abstract

The tumor suppressor protein PML and oncoprotein MDM2 have opposing effects on p53. PML stimulates p53 activity by recruiting it to nuclear foci termed PML nuclear bodies. In contrast, MDM2 inhibits p53 by promoting its degradation. To date, neither a physical nor functional relationship between PML and MDM2 has been described. In this study, we report an in vivo and in vitro interaction between PML and MDM2 which is independent p53. PML which The by MDM2 which MDM2 In PML which and PML in which an this a MDM2 a PML to and this PML and MDM2 interaction between PML and MDM2 PML nuclear MDM2 PML to activity a MDM2 MDM2 and PML protein and have effects on activity The tumor suppressor protein PML and oncoprotein MDM2 have opposing effects on p53. PML stimulates p53 activity by recruiting it to nuclear foci termed PML nuclear bodies. In contrast, MDM2 inhibits p53 by promoting its degradation. To date, neither a physical nor functional relationship between PML and MDM2 has been described. In this study, we report an in vivo and in vitro interaction between PML and MDM2 which is independent p53. PML which The by MDM2 which MDM2 In PML which and PML in which an this a MDM2 a PML to and this PML and MDM2 interaction between PML and MDM2 PML nuclear MDM2 PML to activity a MDM2 MDM2 and PML protein and have effects on activity PML is a tumor suppressor and nuclear The PML a a The The PML on and nuclear nuclear nuclear nuclear on and is in in and The PML is its to nuclear foci have been termed PML nuclear PML in and and The In and a PML to a nuclear PML PML by inhibits activity PML protein in its a to an a PML is by a is to on PML and in an to its degradation. in in in and in nuclear The PML is and its to to this by a in which a PML in its to by which PML a tumor suppressor and inhibits have been a PML an to in to PML a in relationship between PML and p53 by p53 PML and by PML have PML p53 and to which p53 and to an PML and p53 In p53 activity in and an in in p53 and In contrast, p53 neither nor in and to PML is p53 in to and activity in by a MDM2 to p53 and inhibits activity p53 a MDM2 p53 and its by p53 to PML and MDM2 have opposing effects on p53 it is to functional relationship between PML and to neither a physical nor functional interaction between PML and MDM2 has been described. The report an in vivo and in vitro interaction between PML and MDM2 which independent p53. PML and MDM2 protein and and activity PML PML this by The and The and and PML by PML and and and PML and a and its and its in and its and The and and in MDM2 and MDM2 and MDM2 MDM2 and by MDM2 a MDM2 and The and and and in MDM2 MDM2 and MDM2 and The and and and in MDM2 and and p53 and MDM2 in and in and in and in to and and The on by a to by and to a an an To PML and and a to to on and and and and PML and MDM2 and a PML by a The and The and and PML by a to and protein by in To by in and The by and MDM2 to MDM2 protein in MDM2 protein by by in by and by and MDM2 MDM2 between and a and in MDM2 protein by a to an and a protein to PML To an in vivo interaction between PML and to to PML and by and MDM2 and between PML and MDM2 in p53 MDM2 and PML an in p53. to PML and MDM2 we have been to PML PML protein is PML and To interaction MDM2 and an and by an in MDM2 in MDM2 and PML in p53. To MDM2 and PML PML protein to in on and MDM2 protein in between PML and MDM2 in in MDM2 a between MDM2 and protein MDM2 and PML and this a MDM2 protein a protein this in vitro between PML and MDM2 MDM2 to PML and MDM2 PML protein a and an To PML MDM2 MDM2 in an and by an in MDM2 PML a interaction MDM2 a PML to in which an by an In PML to PML and a to PML between and a MDM2 and PML to this PML to PML protein and MDM2 and PML PML protein an and an MDM2 and MDM2 by and The in protein is to MDM2 an MDM2 in and MDM2 protein an and an and MDM2 by and PML is by a in PML and The is by and interaction between and PML The The PML an MDM2 PML to To this PML in which to in and between and MDM2 by in MDM2 PML to a in MDM2 PML and PML to a In contrast, PML and PML a MDM2 PML PML an MDM2 In we to PML PML is to in a and by an a PML and to PML is In contrast, PML To PML to PML and an and by an In and PML a MDM2 and PML PML is PML MDM2 and to MDM2 to PML MDM2 and PML PML protein an and an MDM2 and MDM2 by and The in and by an The PML and The which MDM2 and an an and an The and PML The in by interaction between and MDM2 to this in PML To this MDM2 by nuclear PML is in between and in a MDM2 in to in a MDM2 in a MDM2 MDM2 a In to MDM2 MDM2 PML and and to to nuclear MDM2 In contrast, and to to MDM2 and The and to in and to a and nuclear MDM2 and MDM2 in a MDM2 PML to to MDM2 in a to in an MDM2 in this PML which an MDM2 PML MDM2 MDM2 an and by an MDM2 The in an PML MDM2 in in between and and a is by and is between and to MDM2 interaction To this MDM2 to a PML which PML MDM2 The in PML which MDM2 a MDM2 PML in which have on PML PML a MDM2 between this PML and an MDM2 between and MDM2 between and interaction between MDM2 and PML a MDM2 MDM2 between and interaction To PML MDM2 in to PML PML In PML a MDM2 MDM2 MDM2 a in In contrast, PML MDM2 between and MDM2 PML to an MDM2 In MDM2 a PML in MDM2 which between and PML The MDM2 and PML in and by and a MDM2 and PML The on between MDM2 and The protein which to PML in between and PML a MDM2 MDM2 MDM2 MDM2 between and The MDM2 to interaction PML interaction an MDM2 this between PML and we to on activity The PML is its nuclear foci PML and to and PML to a tumor suppressor To MDM2 on PML PML PML and MDM2 by in and MDM2 to In contrast, MDM2 a PML to MDM2 protein nuclear nuclear MDM2 a PML to to which PML to and in to MDM2 which to this nuclear in and MDM2 p53 nuclear neither nor p53 is this in MDM2 PML nuclear in p53. MDM2 to PML nuclear and PML to MDM2 this this an PML to nuclear MDM2 PML between PML and MDM2 is to nuclear nuclear PML in and by and and MDM2 nuclear and MDM2 and by The in in The and MDM2 nuclear in in which MDM2 nuclear protein which PML is PML has been to a protein to a to MDM2 PML to in MDM2 PML to on activity MDM2 PML to To MDM2 this we MDM2 to PML in this in MDM2 PML to between MDM2 and PML is to PML in this MDM2 is to PML nuclear nuclear is MDM2 to PML to In contrast, an MDM2 to on PML to MDM2 to PML in this MDM2 and between MDM2 and inhibits and MDM2 a and and MDM2 activity by protein The to independent tumor suppressor protein PML has in to its in and its interaction p53. PML p53 to to foci The is to p53 activity a to p53 in p53 by p53 to an p53 to tumor suppressor In to PML a and in in and protein and and in and on have been report MDM2 a between PML and MDM2 in in MDM2 PML in and MDM2 in a a MDM2 and PML in a independent p53 and this a MDM2 and PML in which MDM2 a The PML is between PML and PML have been which in and by in to interaction MDM2 is an activity by PML in an The MDM2 a in PML The PML and MDM2 a and we interaction between PML is to MDM2 this interaction MDM2 is to which MDM2 PML in PML PML protein PML in to is PML which MDM2 is this this PML to it is PML The is by PML is nuclear foci PML to to in PML is The and nuclear In its and is MDM2 and a PML to in PML it is MDM2 PML this its The MDM2 is to PML and PML is PML to to by MDM2 and interaction between PML and MDM2 between is is to and PML MDM2 is to on a and in PML is to The has been in to and a The In contrast, PML and to and on it has been and PML a in a PML to and protein The and a and protein a and to PML MDM2 a in is a activity and is a PML a and this stimulates a protein to In MDM2 PML to between MDM2 and PML is to PML in this MDM2 and to PML to PML to nuclear PML is MDM2 to in this and to p53. PML p53 and to in an p53 to an p53 to tumor suppressor MDM2 this p53 by PML to a to p53. PML is a tumor suppressor and nuclear The PML a a The The PML on and nuclear nuclear nuclear nuclear on and is in in and The PML is its to nuclear foci have been termed PML nuclear PML in and and The In and a PML to a nuclear PML PML by inhibits activity The PML protein in its a to an a PML is by a is to on PML and in an to its degradation. in in in and in nuclear The PML is and its to to this by a in which a PML in its to The by which PML a tumor suppressor and inhibits have been a PML an to in to PML a in relationship between PML and p53 by p53 PML and by PML have PML p53 and to which p53 and to an PML and p53 In p53 activity in and an in in p53 and In contrast, p53 neither nor in and to PML is p53 in to p53 and activity in by a MDM2 to p53 and inhibits activity p53 a MDM2 p53 and its by p53 to PML and MDM2 have opposing effects on p53 it is to functional relationship between PML and to neither a physical nor functional interaction between PML and MDM2 has been described. The report an in vivo and in vitro interaction between PML and MDM2 which independent p53. 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PML p53 and to in an p53 to an p53 to tumor suppressor MDM2 this p53 by PML to a to p53. The tumor suppressor protein PML has in to its in and its interaction p53. PML p53 to to foci The is to p53 activity a to p53 in p53 by p53 to an p53 to tumor suppressor In to PML a and in in and protein and and in and on have been The report MDM2 a between PML and MDM2 in in MDM2 PML in and MDM2 in a a MDM2 and PML in a independent p53 and this a MDM2 and PML in which MDM2 a The PML is between PML and PML have been which in and by in to interaction MDM2 is an activity by PML in an The MDM2 a in PML The PML and MDM2 a and we interaction between PML is to MDM2 this interaction MDM2 is to which MDM2 PML in PML PML protein PML in to is PML which MDM2 is this this PML to it is PML The is by PML PML is nuclear foci PML to to in PML is The and nuclear In its and is MDM2 and a PML to in PML it is MDM2 PML this its The MDM2 is to PML and PML is PML to to by MDM2 and interaction between PML and MDM2 between is is to and PML MDM2 is to on a and in PML is to The has been in to and a The In contrast, PML and to and on it has been and PML a in a PML to and protein The and a and protein a and to PML MDM2 a in is a activity and is a PML a and this stimulates a protein to In MDM2 PML to between MDM2 and PML is to PML in this MDM2 and to PML to PML to nuclear PML is MDM2 to in this and to p53. PML p53 and to in an p53 to an p53 to tumor suppressor MDM2 this p53 by PML to a to p53.