p73-dependent expression of DAN during cisplatin-induced cell death and osteoblast differentiation.
We previously reported that DAN, a founding member of the DAN family of secreted proteins, acts as an inhibitor of cell cycle progression and is closely involved in retinoic acid-induced neuroblastoma differentiation. In this study, we found that DAN as well as p73, the recently identified p53 family member, was up-regulated during osteoblast differentiation. Additionally, the expression of DAN was increased in response to cisplatin-induced cell death of neuroblastoma SH-SY5Y cells. Consistent with the previous reports, p73 was accumulated after the treatment with cisplatin. Intriguingly, we found a putative p53/p73-binding site in the 5'-upstream region of the human DAN gene. A luciferase reporter assay and an in vitro DNA-binding experiment revealed that this canonical p53/p73-binding site was a functional responsive element and was specific for p73. Our results suggest that there exists a functional association between DAN and p73 during osteoblast differentiation as well as cisplatin-induced cell death.
Shinbo
Jun
J
Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba 260-8717, Japan.
Ozaki
Toshinori
T
Nakagawa
Takahito
T
Watanabe
Ken-ichi
K
Nakamura
Yohko
Y
Yamazaki
Masashi
M
Moriya
Hideshige
H
Nakagawara
Akira
A
Sakiyama
Shigeru
S
D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology*; D016207:Cytokines; D004247:DNA; D004268:DNA-Binding Proteins / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
D018797:Cell Cycle Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; C490088:Grem2 protein, mouse; C490087:NBL1 protein, human; C490089:Nbl1 protein, mouse; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D004247:DNA; D002945:Cisplatin