SUMO-1 Modification of PIASy, an E3 Ligase, Is Necessary for PIASy-Dependent Activation of Tcf-4
- 1 May 2005
- journal article
- research article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 25 (9), 3506-3518
- https://doi.org/10.1128/mcb.25.9.3506-3518.2005
Abstract
We have previously shown that modification of Tcf-4, a transcription factor in the Wnt pathway, with SUMO by PIASy, a SUMO E3 ligase, enhances its transcriptional activity. Since PIASy itself was also modified with SUMO-1, we studied the role of sumoylation of PIASy in the regulation of Tcf-4. Lys35 was found to be a sumoylation site of PIASy. PIASyK35R, in which Lys35 was mutated to Arg, did not enhance sumoylation of Tcf-4, although this PIASy mutant did not lose the ligase activity of sumoylation for other proteins. Wild-type PIASy and PIASyK35R showed a distinct distribution in the nucleus, although both were colocalized with Tcf-4. Promyelocytic leukemia protein, which is involved in transcriptional regulation, was associated with PIASyK35R more frequently than wild-type PIASy in the nucleus. PIASyK35R could not stimulate the transcriptional activity of Tcf-4 under the conditions in which wild-type PIASy enhanced it. Conjugation of SUMO-1 to the amino terminus of PIASyK35R neither enhanced sumoylation of Tcf-4 nor stimulated the transcriptional activity of Tcf-4. These results suggest that sumoylation of Lys35 in PIASy determines the nuclear localization of PIASy and that it is necessary for PIASy-dependent sumoylation and transcriptional activation of Tcf-4.Keywords
This publication has 43 references indexed in Scilit:
- SUMO and ubiquitin in the nucleus: different functions, similar mechanisms?Genes & Development, 2004
- SUMO modification of a novel MAR-binding protein, SATB2, modulates immunoglobulin μ gene expressionGenes & Development, 2003
- The Polycomb Protein Pc2 Is a SUMO E3Cell, 2003
- Casein Kinase Iε Enhances the Binding of Dvl-1 to Frat-1 and Is Essential for Wnt-3a-induced Accumulation of β-CateninJournal of Biological Chemistry, 2003
- PIAS Proteins Modulate Transcription Factors by Functioning as SUMO-1 LigasesMolecular and Cellular Biology, 2002
- Ubc9p and the conjugation of SUMO-1 to RanGAP1 and RanBP2Current Biology, 1998
- Conjugation with the ubiquitin-related modifier SUMO-1 regulates the partitioning of PML within the nucleusThe EMBO Journal, 1998
- Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC −/− Colon CarcinomaScience, 1997
- A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex.The Journal of cell biology, 1996
- Epithelial cytoskeletal framework and nuclear matrix-intermediate filament scaffold: three-dimensional organization and protein composition.The Journal of cell biology, 1984