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Genes & Dev. 15 (23): 3088-3103

Copyright © 2001 by Cold Spring Harbor Laboratory Press.

Vol. 15, No. 23, pp. 3088-3103, December 1, 2001

RESEARCH PAPER
PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies

Shrikesh Sachdev,1 Laurakay Bruhn,1 Heidemarie Sieber,1 Andrea Pichler,2 Frauke Melchior,2 and Rudolf Grosschedl1,3

1 Gene Center and Institute of Biochemistry, University of Munich, 81377 Munich, Germany; and 2 Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany

The Wnt-responsive transcription factor LEF1 can activate transcription in association with beta -catenin and repress transcription in association with Groucho. In search of additional regulatory mechanisms of LEF1 function, we identified the protein inhibitor of activated STAT, PIASy, as a novel interaction partner of LEF1. Coexpression of PIASy with LEF1 results in potent repression of LEF1 activity and in covalent modification of LEF1 with SUMO. PIASy markedly stimulates the sumoylation of LEF1 and multiple other proteins in vivo and functions as a SUMO E3 ligase for LEF1 in a reconstituted system in vitro. Moreover, PIASy binds to nuclear matrix-associated DNA sequences and targets LEF1 to nuclear bodies, suggesting that PIASy-mediated subnuclear sequestration accounts for the repression of LEF1 activity.

[Key Words: PIAS; SUMO; LEF1/TCF; nuclear matrix; PML bodies]


3 Corresponding author.


GENES & DEVELOPMENT 15:3088-3103 © 2001 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/01 $5.00


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S. Palacios, L. H. Perez, S. Welsch, S. Schleich, K. Chmielarska, F. Melchior, and J. K. Locker (2005)
Mol. Biol. Cell 16, 2822-2835
   Abstract »    Full Text »    PDF »
SUMO Represses Transcriptional Activity of the Drosophila SoxNeuro and Human Sox3 Central Nervous System-specific Transcription Factors.
J. Savare, N. Bonneaud, and F. Girard (2005)
Mol. Biol. Cell 16, 2660-2669
   Abstract »    Full Text »    PDF »
Sumoylation induced by the Arf tumor suppressor: A p53-independent function.
K. Tago, S. Chiocca, and C. J. Sherr (2005)
PNAS 102, 7689-7694
   Abstract »    Full Text »    PDF »
SUMO-1 Modification of PIASy, an E3 Ligase, Is Necessary for PIASy-Dependent Activation of Tcf-4.
M. Ihara, H. Yamamoto, and A. Kikuchi (2005)
Mol. Cell. Biol. 25, 3506-3518
   Abstract »    Full Text »    PDF »
Ikaros SUMOylation: Switching Out of Repression.
P. Gomez-del Arco, J. Koipally, and K. Georgopoulos (2005)
Mol. Cell. Biol. 25, 2688-2697
   Abstract »    Full Text »    PDF »
Repression and Coactivation of CCAAT/Enhancer-binding Protein {epsilon} by Sumoylation and Protein Inhibitor of Activated STATx Proteins.
J. Kim, S. Sharma, Y. Li, E. Cobos, J. J. Palvimo, and S. C. Williams (2005)
J. Biol. Chem. 280, 12246-12254
   Abstract »    Full Text »    PDF »
Association with Class IIa Histone Deacetylases Upregulates the Sumoylation of MEF2 Transcription Factors.
S. Gregoire and X.-J. Yang (2005)
Mol. Cell. Biol. 25, 2273-2287
   Abstract »    Full Text »    PDF »
The DEAD-Box Protein DP103 (Ddx20 or Gemin-3) Represses Orphan Nuclear Receptor Activity via SUMO Modification.
M. B. Lee, L. A. Lebedeva, M. Suzawa, S. A. Wadekar, M. Desclozeaux, and H. A. Ingraham (2005)
Mol. Cell. Biol. 25, 1879-1890
   Abstract »    Full Text »    PDF »
Role for SUMO Modification in Facilitating Transcriptional Repression by BKLF.
J. Perdomo, A. Verger, J. Turner, and M. Crossley (2005)
Mol. Cell. Biol. 25, 1549-1559
   Abstract »    Full Text »    PDF »
Negative Regulation of NF-{kappa}B Signaling by PIAS1.
B. Liu, R. Yang, K. A. Wong, C. Getman, N. Stein, M. A. Teitell, G. Cheng, H. Wu, and K. Shuai (2005)
Mol. Cell. Biol. 25, 1113-1123
   Abstract »    Full Text »    PDF »
Multiple activities contribute to Pc2 E3 function.
M. H. Kagey, T. A. Melhuish, S. E. Powers, and D. Wotton (2005)
EMBO J. 24, 108-119
   Abstract »    Full Text »    PDF »
Sumoylation of MITF and Its Related Family Members TFE3 and TFEB.
A. J. Miller, C. Levy, I. J. Davis, E. Razin, and D. E. Fisher (2005)
J. Biol. Chem. 280, 146-155
   Abstract »    Full Text »    PDF »
p53-Dependent and -Independent Functions of the Arf Tumor Suppressor.
C.J. SHERR, D. BERTWISTLE, W. DEN BESTEN, M.-L. KUO, M. SUGIMOTO, K. TAGO, R.T. WILLIAMS, F. ZINDY, and M.F. ROUSSEL (2005)
Cold Spring Harb Symp Quant Biol 70, 129-137
   Abstract »    PDF »
A Universal Strategy for Proteomic Studies of SUMO and Other Ubiquitin-like Modifiers.
G. Rosas-Acosta, W. K. Russell, A. Deyrieux, D. H. Russell, and V. G. Wilson (2005)
Mol. Cell. Proteomics 4, 56-72
   Abstract »    Full Text »    PDF »
Regulation and Function of SUMO Modification.
R. S. Hilgarth, L. A. Murphy, H. S. Skaggs, D. C. Wilkerson, H. Xing, and K. D. Sarge (2004)
J. Biol. Chem. 279, 53899-53902
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Nuclear translocation of an ICA512 cytosolic fragment couples granule exocytosis and insulin expression in {beta}-cells.
M. Trajkovski, H. Mziaut, A. Altkruger, J. Ouwendijk, K.-P. Knoch, S. Muller, and M. Solimena (2004)
J. Cell Biol. 167, 1063-1074
   Abstract »    Full Text »    PDF »

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