Induction of p73β by a naphthoquinone analog is mediated by E2F‐1 and triggers apoptosis in HeLa cells

FEBS Letters

Choi, Kyung Hee²  Kim, Mie-Young³  Lee, Jung-Hee²  Kim, Keun-Cheol²  Ham, Seung-Wook¹  Kang, Kyung-Hwa² 

[1] Department of Chemistry, College of Natural Sciences, Chung-Ang University, Seoul 156-756, South Korea;Department of Biology, College of Natural Sciences, Chung-Ang University, Heuksuk-dong 221, Dongjak-ku, Seoul 156-756, South Korea;Division of Biochemistry, College of Pharmacy, Chung-Ang University, Seoul 156-756, South Korea

关键词: p73β;    Naphthoquinone analog;    Apoptosis;    E2F-1;    NA;    naphthoquinone analog;    GFP;    green fluorescent protein;   

DOI  :  10.1016/S0014-5793(02)02921-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Recently, p73 was identified as a structural and functional homolog of p53. The p73 protein activates the transcription of genes downstream of p53 and induces apoptosis when overexpressed in several cell lines, similar to the tumor suppressor p53. However, the extracellular stimuli and molecular mechanisms regulating p73 activity remain to be elucidated. In this paper, we present evidence that the naphthoquinone analog, 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (NA), is a novel apoptotic stimulus that induces p73β expression. Treatment with NA induced the expression of p73β mRNA and protein and its downstream genes, p21 and bax, in HeLa cells. Similar results were obtained in MCF7 cells (p53^+/+, p73^+/+). In the MCF7 cells, p53 protein level was rather decreased by NA treatment. Overexpression of p73β led to the apoptosis of HeLa cells and enhancement of NA-induced cell death. Expression of p73β was mediated by E2F-1, which was activated via release from pRB after exposure of cells to NA. We additionally observed that overexpression of pRB inhibited NA-induced apoptosis. These results imply that p53-independent p73β-dependent p21 expression is involved in NA-induced apoptosis of HeLa cells.

【 授权许可】

Unknown