tailieunhanh - Báo cáo khoa học: Two short protein domains are responsible for the nuclear localization of the mouse spermine oxidase l isoform

In mouse, at least two catalytically active splice variants (mSMOaand mSMOl) of the flavin-containing spermine oxidase enzyme are present. We have demonstrated previously that the cytosolic mSMOais the major iso-form, while the mSMOlenzyme is present in both nuclear and cytoplasmic compartments and has an extra protein domain corresponding to the addi-tional exon VIa. | iFEBS Journal Two short protein domains are responsible for the nuclear localization of the mouse spermine oxidase I isoform Marzia Bianchi1 Roberto Amendola2 Rodolfo Federico1 Fabio Polticelli1 and Paolo Mariottini1 1 Dipartimento di Biologia Universita Roma Tre Roma Italy 2 Istituto per la Radioprotezione ENEA CR Casaccia Roma Italy Keywords mouse nuclear localization polyamine oxidase polyamines spermine oxidase Correspondence P. Mariottini Dipartimento di Biologia University degli Studi Roma Tre Viale Guglielmo Marconi 446 00146 Roma Italy Fax 39 06 55176321 Tel 39 06 55176359 E-mail mariotpa@ Received 18 February 2005 revised 7 April 2005 accepted 13 April 2005 In mouse at least two catalytically active splice variants mSMOa and mSMOit of the flavin-containing spermine oxidase enzyme are present. We have demonstrated previously that the cytosolic mSMOa is the major isoform while the mSMOi enzyme is present in both nuclear and cytoplasmic compartments and has an extra protein domain corresponding to the additional exon VIa. By amino acid sequence comparison and molecular modeling of mSMO proteins we identified a second domain that is necessary for nuclear localization of the mSMOi splice variant. A deletion mutant enzyme of this region was constructed to demonstrate its role in protein nuclear targeting by means of transient expression in the murine neuroblastoma cell line N18TG2. doi The polyamines putrescine Put spermine Spm and spermidine Spd are aliphatic amines that are positively charged under physiological conditions and have been shown to be involved in major cellular processes such as cell growth and proliferation 1 2 . The concerted actions of Spd Spm N1-acetyl-transferase vertebrate polyamine oxidase PAO EC and spermine oxidase SMO are involved in maintaining polyamine homeostasis in mammalian cells. The cytosolic Spd Spm N1-acetyl-transferase enzyme is responsible for adding N1-acetyl groups .