Published online before print May 15, 2003, doi: 10.1161/01.RES.0000076893.70898.36
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2003 American Heart Association, Inc.
Molecular Medicine |
Modification of GATA-2 Transcriptional Activity in Endothelial Cells by the SUMO E3 Ligase PIASy
From the Department of Medicine and Clinical Science (T.C., H.I., K.N.), Kyoto University Graduate School of Medicine, Kyoto, Japan, and Departments of Pharmacology (L.S., J.I.) and Internal Medicine (T.C., S.W.), University of Michigan Medical Center, Ann Arbor, Mich.
Correspondence to Tae-Hwa Chun, 5240 MSRBIII, 1150 W Medical Center Dr, Ann Arbor, MI 48109. E-mail taehwa{at}umich.edu
GATA sequences are required for the optimal expression of endothelial cell–specific genes, including endothelin-1 (ET-1). We have identified PIASy in a search for new GATA-2 interacting proteins that can regulate GATA-2–mediated endothelial gene expression. Notably, among the cell populations comprising vascular walls, PIASy mRNA is selectively expressed in endothelial cells, and its expression can be regulated by angiogenic growth factors. We show that GATA-2 is covalently modified by small ubiquitin-like modifier (SUMO)-1 and -2 and that PIASy, through its E3 SUMO ligase activity, preferentially enhances the conjugation of SUMO-2 to GATA-2. Through a functional analysis, we demonstrate that PIASy potently suppresses the activity of the GATA-2–dependent human ET-1 promoter in endothelial cells. The suppressive effect of PIASy requires the GATA-binding site in the ET-1 promoter and depends on its interaction with GATA-2, which requires both N-terminal (amino acids 1-183) and C-terminal (amino acids 414-510) sequences in PIASy. We conclude that PIASy enhances the conjugation of SUMO-2 to GATA-2 and that the interaction of PIASy with GATA-2 can modulate GATA-mediated ET-1 transcription activity in endothelial cells through a RING-like domain-independent mechanism.
Key Words: GATA-2 • endothelin-1 • SUMO ligase • PIAS family
This article has been cited by other articles:
 |
|
 |
|
  C. Figueroa-Romero, J. A. Iniguez-Lluhi, J. Stadler, C.-R. Chang, D. Arnoult, P. J. Keller, Y. Hong, C. Blackstone, and E. L. Feldman SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle FASEB J, November 1, 2009; 23(11): 3917 - 3927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mukherjee, M. Thomas, N. Dadgar, A. P. Lieberman, and J. A. Iniguez-Lluhi Small Ubiquitin-like Modifier (SUMO) Modification of the Androgen Receptor Attenuates Polyglutamine-mediated Aggregation J. Biol. Chem., August 7, 2009; 284(32): 21296 - 21306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-H. Yang, J. H. Heaton, H. Brevig, S. Mukherjee, J. A. Iniguez-Lluhi, and G. D. Hammer SUMOylation Inhibits SF-1 Activity by Reducing CDK7-Mediated Serine 203 Phosphorylation Mol. Cell. Biol., February 1, 2009; 29(3): 613 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Holmstrom, S. Chupreta, A. Y.-L. So, and J. A. Iniguez-Lluhi SUMO-Mediated Inhibition of Glucocorticoid Receptor Synergistic Activity Depends on Stable Assembly at the Promoter But Not on DAXX Mol. Endocrinol., September 1, 2008; 22(9): 2061 - 2075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Viger, S. M. Guittot, M. Anttonen, D. B. Wilson, and M. Heikinheimo Role of the GATA Family of Transcription Factors in Endocrine Development, Function, and Disease Mol. Endocrinol., April 1, 2008; 22(4): 781 - 798. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhao, B. Zheng, Y. Huang, D. Yang, S. Katzman, C. Chang, D. Fowell, and W.-p. Zeng Interaction between GATA-3 and the Transcriptional Coregulator Pias1 Is Important for the Regulation of Th2 Immune Responses J. Immunol., December 15, 2007; 179(12): 8297 - 8304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chupreta, H. Brevig, L. Bai, J. L. Merchant, and J. A. Iniguez-Lluhi Sumoylation-dependent Control of Homotypic and Heterotypic Synergy by the Kruppel-type Zinc Finger Protein ZBP-89 J. Biol. Chem., December 14, 2007; 282(50): 36155 - 36166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Herrmann, L. O. Lerman, and A. Lerman Ubiquitin and Ubiquitin-Like Proteins in Protein Regulation Circ. Res., May 11, 2007; 100(9): 1276 - 1291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. van den Akker, S. Ano, H.-M. Shih, L.-C. Wang, M. Pironin, J. J. Palvimo, N. Kotaja, O. Kirsh, A. Dejean, and J. Ghysdael FLI-1 Functionally Interacts with PIASx{alpha}, a Member of the PIAS E3 SUMO Ligase Family J. Biol. Chem., November 11, 2005; 280(45): 38035 - 38046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Morita, C. Kanei-Ishii, T. Nomura, and S. Ishii TRAF7 Sequesters c-Myb to the Cytoplasm by Stimulating Its Sumoylation Mol. Biol. Cell, November 1, 2005; 16(11): 5433 - 5444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Minegishi, N. Suzuki, Y. Kawatani, R. Shimizu, and M. Yamamoto Rapid turnover of GATA-2 via ubiquitin-proteasome protein degradation pathway Genes Cells, July 1, 2005; 10(7): 693 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chupreta, S. Holmstrom, L. Subramanian, and J. A. Iniguez-Lluhi A Small Conserved Surface in SUMO Is the Critical Structural Determinant of Its Transcriptional Inhibitory Properties Mol. Cell. Biol., May 15, 2005; 25(10): 4272 - 4282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, X.-h. Feng, and R. J. Schwartz SUMO-1 Modification Activated GATA4-dependent Cardiogenic Gene Activity J. Biol. Chem., November 19, 2004; 279(47): 49091 - 49098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Collavin, M. Gostissa, F. Avolio, P. Secco, A. Ronchi, C. Santoro, and G. Del Sal Modification of the erythroid transcription factor GATA-1 by SUMO-1 PNAS, June 15, 2004; 101(24): 8870 - 8875. [Abstract] [Full Text] [PDF]
|
|