Age associated high level of major vault protein is p53 dependent.
Major vault protein (MVP) represents the main component of vaults and has been linked to multi-drug resistance (MDR) in cancer cells. We previously reported that MVP plays an important role in the resistance of senescent human diploid fibroblasts (HDFs) to apoptosis and also that MVP expression is markedly reduced in young HDFs but not in senescent HDFs. In this study, designed to elucidate the regulation of MVP in young and senescent HDFs, we examined the levels of transcriptional factors for the MVP gene, which revealed that among the putative transcriptional factors, p53 decreased only in young HDFs, but not in senescent HDFs in response to H(2)O(2) treatment in the same mode as the expression of MVP. Moreover, the phosphorylation status of p53 increased only in senescent HDFs but not in young HDFs in response to H(2)O(2) treatment. Therefore, we tested the possibility of MVP regulation by p53 status. MVP is upregulated in p53 over-expressing young HDFs, while MVP is downregulated in p53-specific small interfering RNA (siRNA)-transfected senescent HDFs, which suggests that the expression of MVP would be p53 dependent. Furthermore, using chromatin immunoprecipitation (ChIP) assay, we observed that p53 binds directly to the MVP promoter. Taken together, these results suggest that p53 would be a major transcriptional factor for MVP gene expression.
An
Hong-Joo
HJ
Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Seoul National University College of Medicine, Korea.
Ryu
Sung-Jin
SJ
Kim
Sung-Young
SY
Choi
Hae-Ri
HR
Chung
Jun-Ho
JH
Park
Sang-Chul
SC
D017209:Apoptosis; D016922:Cellular Senescence; D004171:Diploidy; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics / Q000378:metabolism*; D000099187:Major Vault Protein
D006861:Hydrogen Peroxide; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein