HMGB2 stabilizes p53 by interfering with E6/E6AP-mediated p53 degradation in human papillomavirus-positive HeLa cells.
We investigated the effect of HMGB2 on the stability of p53 protein in HeLa cells. Overexpression of HMGB2 led to accumulation of the p53 protein, whereas HMGB2 knockdown with siRNA resulted in a substantial decrease in the p53 protein level. The HMGB2-dependent increase of p53 stability was specific for HPV-positive HeLa cells as HCT116 and MCF7 cell lines did not demonstrate this response. Co-expression of HMGB2 and HPV E6 prevented HPV E6 protein-mediated ubiquitination and degradation of p53. FACS analysis exhibited that HeLa cells transfected with HMGB2 displayed decreased cell proliferation, with a concomitant increase of the p53 protein and arrest of the cell cycle, predominantly in G1 phase. Our findings collectively suggest that HMGB2 could stabilize p53 by interfering with E6/E6AP-mediated p53 degradation in HPV-positive HeLa cells.
Lee
Daekyun
D
Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
Kwon
Jung-Hee
JH
Kim
Eui Ho
EH
Kim
Eung-Sam
ES
Choi
Kwan Yong
KY
D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D024261:HMGB2 Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000494:pharmacology; D006367:HeLa Cells / Q000187:drug effects / Q000821:virology*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000494:pharmacology*; D055550:Protein Stability / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects
D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D024261:HMGB2 Protein; D009856:Oncogene Proteins, Viral; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53