Desumoylation of homeodomain-interacting protein kinase 2 (HIPK2) through the cytoplasmic-nuclear shuttling of the SUMO-specific protease SENP1.
The modification of homeodomain-interacting protein kinase 2 (HIPK2) by small ubiquitin-like modifier 1 (SUMO-1) plays an important role in its targeting into the promyelocytic leukemia body, as well as in its differential interaction with binding partner, but the desumoylation of HIPK2 by SUMO-specific proteases is largely unknown. In this study, we show that HIPK2 is a desumoylation target for the SUMO-specific protease SENP1 that shuttles between the cytoplasm and the nucleus. Mutation analyses reveal that SENP1 contains the nuclear export sequence (NES) within the extreme carboxyl-terminal region, and SENP1 is exported to the cytoplasm in a NES-dependent manner. Sumoylated HIPK2 are deconjugated by SENP1 both in vitro and in cultured cells, and the desumoylation is enhanced either by the forced translocation of SENP1 into the nucleus or by the SENP1 NES mutant. Concomitantly, desumoylation induces dissociation of HIPK2 from nuclear bodies. These results demonstrate that HIPK2 is a target for SENP1 desumoylation, and suggest that the desumoylation of HIPK2 may be regulated by the cytoplasmic-nuclear shuttling of SENP1.
Kim
Young Ho
YH
Laboratory Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Sung
Ki Sa
KS
Lee
Sook-Jeong
SJ
Kim
Yong-Ou
YO
Choi
Cheol Yong
CY
Kim
Yongsok
Y
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000737:chemistry / Q000201:enzymology*; D003546:Cysteine Endopeptidases; D003593:Cytoplasm / Q000737:chemistry / Q000201:enzymology; D010450:Endopeptidases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D049790:Nuclear Export Signals; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D049790:Nuclear Export Signals; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases