ABSTRACT
The retinoblastoma (RB) tumor suppressor protein, pRB, plays an important role in the regulation of mammalian cell cycle. Furthermore, several lines of evidence suggest that pRB also involves in the regulation of apoptosis. In the present study, the degradation of pRB was observed in apoptotic gastric tumor cells treated with a new potent anti-tumor component, tripchlorolide (TC). The inhibition of pRB degradation by a general cysteine protease inhibitor IDAM resulted in the reduction of the apoptotic cells. Furthermore, the survival of the gastric tumor cells under the TC treatment was enhanced by an over-expression of exogenous pRB. These results suggest that the pRB degradation of the gastric tumor cells under the TC treatment involves in the apoptotic progression. In addition, the same extent of TC-induced pRB-degradation was detected in the gastric tumor cells containing a p53 dominant-negative construct, indicating that this kind of pRB degradation is p53-independent.
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Acknowledgements
We thank Dr. Yuan Chao LI of Institute of Materia Medica, SIBS, CAS who kindly provided TC compound. We thank Dr. Xue Liang ZHU of Institute of Biochemistry and Cell Biology, SIBS, CAS who kindly provided p44-2L RB plasmid. This work was supported by a grant of National Natural Science Foundation #30230110, a grant of Science and Technology Commission of Shanghai Municipality #04DZ14901, a grant of Chinese Academy of Sciences #KSCX2-SW-203, and a grant of the Shanghai-Hong Kong-Anson Research Foundation for CAS and CUHK (Chinese University of Hong Kong) in Molecular Biosciences (SHARF) to Jia Rui WU.
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JIN, Y., LEUNG, W., SUNG, JY. et al. p53-independent pRB degradation contributes to a drug-induced apoptosis in AGS cells. Cell Res 15, 695–703 (2005). https://doi.org/10.1038/sj.cr.7290339
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DOI: https://doi.org/10.1038/sj.cr.7290339
