Covalent modification of human homeodomain interacting protein kinase 2 by SUMO-1 at lysine 25 affects its stability

被引:41
作者
Gresko, E [1 ]
Möller, A [1 ]
Roscic, A [1 ]
Schmitz, ML [1 ]
机构
[1] Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland
关键词
HIPK2; SUMO-1; Ubc9; p53;
D O I
10.1016/j.bbrc.2005.02.113
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
The HIPK2 protein is a critical regulator of apoptosis and functionally interacts with p53 to increase gene expression. Here we show that human HIPK2 is modified by sumoylation at lysine 25, as revealed by in vivo and in vitro experiments. While SUMO-1 modification of HIPK2 has no influence on its ability to phosphorylate p53 at serine 46, to induce gene expression, and to mediate apoptosis, a non-sumoylatable HIPK2 mutant displays a strongly increased protein stability. The N-terminal SUMO-1 modification site is conserved between all vertebrate HIPK2 proteins and is found in all members of the HIPK family of protein kinases. Accordingly, also human HIPK3 is modified by sumoylation. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:1293 / 1299
页数:7
相关论文
共 32 条
[1]   Covalent attachment of the SUMO-1 protein to the negative regulatory domain of the c-Myb transcription factor modifies its stability and transactivation capacity [J].
Bies, J ;
Markus, J ;
Wolff, L .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (11) :8999-9009
[2]   Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis [J].
D'Orazi, G ;
Cecchinelli, B ;
Bruno, T ;
Manni, I ;
Higashimoto, Y ;
Saito, S ;
Gostissa, M ;
Coen, S ;
Marchetti, A ;
Del Sal, G ;
Piaggio, G ;
Fanciulli, M ;
Appella, E ;
Soddu, S .
NATURE CELL BIOLOGY, 2002, 4 (01) :11-19
[3]   The protein stability and transcriptional activity of p63α are regulated by SUMO-1 conjugation [J].
Ghioni, P ;
D'Alessandra, Y ;
Mansueto, G ;
Jaffray, E ;
Hay, RT ;
La Mantia, G ;
Guerrini, L .
CELL CYCLE, 2005, 4 (01) :183-190
[4]   SUMO and ubiquitin in the nucleus: different functions, similar mechanisms? [J].
Gill, G .
GENES & DEVELOPMENT, 2004, 18 (17) :2046-2059
[5]   p300 transcriptional repression is mediated by SUMO modification [J].
Girdwood, D ;
Bumpass, D ;
Vaughan, OA ;
Thain, A ;
Anderson, LA ;
Snowden, AW ;
Garcia-Wilson, E ;
Perkins, ND ;
Hay, RT .
MOLECULAR CELL, 2003, 11 (04) :1043-1054
[6]   SUMO and transcriptional regulation [J].
Girdwood, DWH ;
Tatham, MH ;
Hay, RT .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2004, 15 (02) :201-210
[7]   Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1 [J].
Gostissa, M ;
Hengstermann, A ;
Fogal, V ;
Sandy, P ;
Schwarz, SE ;
Scheffner, M ;
Del Sal, G .
EMBO JOURNAL, 1999, 18 (22) :6462-6471
[8]   Requirement of the co-repressor homeodomain-interacting protein kinase 2 for Ski-mediated inhibition of bone morphogenetic protein-induced transcriptional activation [J].
Harada, J ;
Kokura, K ;
Kanei-Ishii, C ;
Nomura, T ;
Khan, MM ;
Kim, Y ;
Ishii, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (40) :38998-39005
[9]   Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2 [J].
Hofmann, TG ;
Möller, A ;
Sirma, H ;
Zentgraf, H ;
Taya, Y ;
Dröge, W ;
Will, H ;
Schmitz, ML .
NATURE CELL BIOLOGY, 2002, 4 (01) :1-10
[10]   Protein modification by SUMO [J].
Johnson, ES .
ANNUAL REVIEW OF BIOCHEMISTRY, 2004, 73 :355-382