Differential interactions of the homeodomain-interacting protein kinase 2 (HIPK2) by phosphorylation-dependent sumoylation.
Homeodomain-interacting protein kinase 2 (HIPK2) interacts with and phosphorylates various transcription factors that are critical regulators of cell fate decisions and apoptosis during development. Here we show that lysine 25 of HIPK2 is the major sumoylation site, both in vitro and in vivo, and that the sumoylation of this site occurs in a phosphorylation-dependent manner. This became clear with the finding that kinase-dead HIPK2 (K221R) could not be efficiently sumoylated in vitro. The sumoylation of HIPK2 resulted in the disruption of its interaction with a Groucho corepressor. Consequently, sumoylation inhibited the regulatory activity of HIPK2 on the Groucho-mediated repression of transcription, whereas not on p53-mediated transactivation. These results suggest that phosphorylation-dependent sumoylation enables HIPK2 to drive different target gene transcription by means of differential interactions with its binding partners.
Sung
Ki Sa
KS
Department of Biological Science, Sungkyunkwan University, 300 Chunchundong, Suwon 440-746, Korea.
Go
Yoon Young
YY
Ahn
Jin-Hyun
JH
Kim
Young Ho
YH
Kim
Yongsok
Y
Choi
Cheol Yong
CY
D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008239:Lysine; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D016159:Tumor Suppressor Protein p53; C091023:gro protein, Drosophila; C115114:HIPK2 protein, human