title: PARP1 regulates the protein stability and proapoptotic function of HIPK2.
abstract: Homeodomain-interacting protein kinase 2 (HIPK2) is a nuclear serine/threonine kinase that functions in DNA damage response and development. In the present study, we propose that the protein stability and proapoptotic function of HIPK2 are regulated by poly(ADP-ribose) polymerase 1 (PARP1). We present evidence indicating that PARP1 promotes the proteasomal degradation of HIPK2. The tryptophan-glycine-arginine (WGR) domain of PARP1 was necessary and sufficient for the promotion of HIPK2 degradation independently of the PARP1 enzymatic activity. The WGR domain mediated the interaction between HIPK2 and C-terminus of HSP70-interacting protein (CHIP) via HSP70. We found that CHIP can function as a ubiquitin ligase for HIPK2. The interaction between PAPR1 and HIPK2 was weakened following DNA damage. Importantly, PARP1 reduced the HIPK2-mediated p53 phosphorylation, proapoptotic transcriptional activity and cell death. These results suggest that PARP1 can modulate the tumor-suppressing function of HIPK2 by regulating the protein stability of HIPK2.
authors: Department of Molecular Biology, Sejong University, Seoul 143-747, Korea.
authors: Jong-Ryoul
authors: JR
authors: Choi
authors: Department of Biology, Kyung Hee University, Seoul 130-701, Korea.|Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Ki Soon
authors: KS
authors: Shin
authors: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Korea.
authors: Cheol Yong
authors: CY
authors: Choi
authors: Department of Molecular Biology, Sejong University, Seoul 143-747, Korea.|Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul 143-747, Korea.
authors: Shin Jung
authors: SJ
authors: Kang
mesh_terms: D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D004249:DNA Damage; D045325:HCT116 Cells; D057809:HEK293 Cells; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D055550:Protein Stability; D059748:Proteolysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018840:HSP70 Heat-Shock Proteins; D016159:Tumor Suppressor Protein p53; C467728:STUB1 protein, human; D044767:Ubiquitin-Protein Ligases; D011065:Poly(ADP-ribose) Polymerases; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases