Scythe/BAT3 regulates apoptotic cell death induced by papillomavirus binding factor in human osteosarcoma.

Abstract

Papillomavirus binding factor (PBF) was first identified as a transcription factor regulating the promoter activity of human papillomavirus. We previously demonstrated that PBF is an osteosarcoma-associated antigen and 92% of osteosarcoma tissues express PBF in the nucleus. Moreover, PBF-positive osteosarcoma has a significantly poorer prognosis than that with negative expression of PBF. In the present study, we assessed the biological role of PBF in cell survival. Overexpression of PBF induced cell death-mediated lactate dehydrase (LDH) release from 293EBNA cells. Cleaved poly(ADP-ribose) polymerase and active caspase-3 were also detected. However, PBF-induced apoptosis did not affect caspase-9 activity. Next, to identify the apoptosis regulator of PBF, we screened a cDNA library constructed from mRNA of the osteosarcoma cell line OS2000 using a yeast two-hybrid system and isolated Scythe/BAT3. Scythe/BAT3 mRNA was detected in 56% of osteosarcoma tissues and ubiquitously in various normal tissues. Although Scythe/BAT3 was localized to the cytoplasm in normal tissue, it was localized to the nucleus in osteosarcoma tissue. PBF and Scythe/BAT3 also colocalized to the cytoplasm in 293T cells and the nucleus in OS2000. Furthermore, overexpression of Scythe/BAT3 suppressed cell death events that resulted from overexpression of PBF in OS2000, but not in 293EBNA cells. Thus, our results support the ideas that: (i) PBF could induce apoptotic cell death via a caspase-9-independent pathway; (ii) the apoptosis regulator Scythe/BAT3 is a PBF-associated molecule acting as a nucleus-cytoplasm shuttling protein; and (iii) colocalization of PBF and Scythe/BAT3 in the nucleus might be an important factor for survival of osteosarcoma cells.

• Authors: Tomohide Tsukahara, Shigeharu Kimura, Shingo Ichimiya, Toshihiko Torigoe, Satoshi Kawaguchi, Takuro Wada, Toshihiko Yamashita, Noriyuki Sato
• Journal: Cancer science (Cancer Sci) Vol. 100 Issue 1 Pg. 47-53 (Jan 2009) ISSN: 1349-7006 [Electronic] England
• PMID: 19018758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BAG6 protein, human
• DNA-Binding Proteins
• Molecular Chaperones
• Proteins
• Transcription Factors
• ZNF395 protein, human
• Caspase 9

Topics

• Apoptosis
• Bone Neoplasms (pathology)
• Caspase 9 (physiology)
• Cell Line, Tumor
• DNA-Binding Proteins (physiology)
• Humans
• Molecular Chaperones
• Osteosarcoma (pathology)
• Proteins (physiology)
• Transcription Factors (physiology)