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

被引:45
作者
Ihara, M [1 ]
Yamamoto, H [1 ]
Kikuchi, A [1 ]
机构
[1] Hiroshima Univ, Grad Sch Biomed Sci, Dept Biochem, Minami Ku, Hiroshima 7348551, Japan
关键词
D O I
10.1128/MCB.25.9.3506-3518.2005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have previously shown that modification of Tcf-4, a transcription factor in the Writ 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. PIASy(K35R), in which Lys(35) 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 colocallized with Tef-4. Promyelocytic leukemia protein, which is involved in transcriptional regulation, was associated with PIASy(K35R) more frequently than wild-type PIASy in the nucleus. PIASy(K35R) 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 PIASy(K35R) neither enhanced sumoylation of Tcf-4 nor stimulated the transcriptional activity of Tcf-4. These results suggest that sumoylation of Lys(35) in PIASy determines the nuclear localization of PIASy and that it is necessary for PIASy-dependent sumoylation and transcriptional activation of Tcf-4.
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页码:3506 / 3518
页数:13
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