SUMO-1 modification of PIASy, an E3 ligase, is necessary for PIASy-dependent activation of Tcf-4

Motomasa Ihara, Hideki Yamamoto, Akira Kikuchi

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48 Citations (Scopus)

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. Lys 35 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.

Original languageEnglish
Pages (from-to)3506-3518
Number of pages13
JournalMolecular and cellular biology
Volume25
Issue number9
DOIs
Publication statusPublished - 2005 May

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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