PIAS1 is an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and acts as a SUMO-tethering factor []. SUMO proteins are ubiquitin like proteins that are covalently attached to and detached from other proteins in cells to modify their function. SUMO is first activated in an ATP-dependent reaction by formation of a thioester bond with an E1 (SUMO-activating) enzyme and then transferred to the SUMO conjugating (E2) enzyme Ubc9. Ubc9 catalyses the formation of an isopeptide bond between the C-terminal of SUMO and the amino group of lysine in the target protein. Sumoylated proteins can be targeted for different cellular processes, such as nuclear transport, transcriptional regulation, apoptosis, and protein stability [].
The SAP motif is a 35-residue motif, which has been named after SAF-A/B,Acinus and PIAS, three proteins known to contain it. The SAP motif is found ina variety of nuclear proteins involved in transcription, DNA repair, RNAprocessing or apoptotic chromatin degradation. As the sap motif of SAF-A hasbeen shown to be essential for specific DNA binding activity, it has beenproposed that it could be a DNA-binding motif [].A multiple alignment of the SAP motif reveals a bipartite distribution ofstrongly conserved hydrophobic, polar and bulky amino acids separated by aregion that contains a glycine. Secondary structure predictions suggest thatthe SAP motif could form two alpha helices separated by a turn [].Some proteins known to contain a SAP motif are listed below:Vertebrate scaffold attachment factors A and B (SAF-A/B). These twoproteins are heterogeneous nuclear ribonucleoproteins (hnRNPs) that bind toAT-rich chromosomal region. It has been proposed that they couple RNAmetabolism to nuclear organisation [, ]. The SAF-A protein is cleaved bycaspase-3 during apoptosis [].Mammalian Acinus, a protein which induces apoptotic chromatin condensationafter cleavage by caspase-3 []. Acinus also contains a RNA-recognitionmotif.Eukaryotic proteins of the PIAS (protein inhibitor of activated STAT)family. These proteins interact with phosphorylated STAT dimers and inhibitSTAT mediated gene activation. Deletion of the first 50 amino acid residuescontaining the SAP domain allows the interaction of PIAS1 with STAT1monomer [].Plant poly(ADP-ribose) polymerase (PARP). PARP is a nuclear protein thatcatalyzes the poly(ADP-ribosyl)ation of proteins. It is involved inresponses to mild and severe oxidative stresses, by mediating DNA repairand programmed cell death processes, respectively []. PARP is tightlybound to chromatin or nuclear matrix.Arabidopsis thaliana Arp, an apurinic endonuclease-redox protein.Yeast THO1 protein. It could be involved in the regulation oftranscriptional elongation by RNA polymerase II [].Animal Ku70. Together with Ku86, it forms a DNA ends binding complex thatis involved in repairing DNA double-strand breaks.Yeast RAD18, a protein involved in DNA repair.Neurospora crassa UVS-2, the homologue of RAD18.
The SAP motif is a 35-residue motif, which has been named after SAF-A/B,Acinus and PIAS, three proteins known to contain it. The SAP motif is found ina variety of nuclear proteins involved in transcription, DNA repair, RNAprocessing or apoptotic chromatin degradation. As the sap motif of SAF-A hasbeen shown to be essential for specific DNA binding activity, it has beenproposed that it could be a DNA-binding motif [].A multiple alignment of the SAP motif reveals a bipartite distribution ofstrongly conserved hydrophobic, polar and bulky amino acids separated by aregion that contains a glycine. Secondary structure predictions suggest thatthe SAP motif could form two alpha helices separated by a turn [].Some proteins known to contain a SAP motif are listed below:Vertebrate scaffold attachment factors A and B (SAF-A/B). These twoproteins are heterogeneous nuclear ribonucleoproteins (hnRNPs) that bind toAT-rich chromosomal region. It has been proposed that they couple RNAmetabolism to nuclear organisation [, ]. The SAF-A protein is cleaved bycaspase-3 during apoptosis [].Mammalian Acinus, a protein which induces apoptotic chromatin condensationafter cleavage by caspase-3 []. Acinus also contains a RNA-recognitionmotif.Eukaryotic proteins of the PIAS (protein inhibitor of activated STAT)family. These proteins interact with phosphorylated STAT dimers and inhibitSTAT mediated gene activation. Deletion of the first 50 amino acid residuescontaining the SAP domain allows the interaction of PIAS1 with STAT1monomer [].Plant poly(ADP-ribose) polymerase (PARP). PARP is a nuclear protein thatcatalyzes the poly(ADP-ribosyl)ation of proteins. It is involved inresponses to mild and severe oxidative stresses, by mediating DNA repairand programmed cell death processes, respectively []. PARP is tightlybound to chromatin or nuclear matrix.Arabidopsis thaliana Arp, an apurinic endonuclease-redox protein.Yeast THO1 protein. It could be involved in the regulation oftranscriptional elongation by RNA polymerase II [].Animal Ku70. Together with Ku86, it forms a DNA ends binding complex thatis involved in repairing DNA double-strand breaks.Yeast RAD18, a protein involved in DNA repair.Neurospora crassa UVS-2, the homologue of RAD18.
