DNA damage-induced inhibition of securin expression is mediated by p53.
Tumor suppressor p53 induces the cellular response to DNA damage mainly by regulating expression of its downstream target genes. The human securin is an anaphase inhibitor, preventing premature chromosome separation through inhibition of separase activity. It is also known as the product of the human pituitary tumor-transforming gene, pttg, a proto-oncogene. Here we report that the expression of human securin is suppressed in cells treated with the DNA-damaging drugs doxorubicin and bleomycin. This suppression requires functional p53. Analysis of the human securin promoter reveals that DNA-binding sites for Sp1 and NF-Y are both required for activation of securin expression; however, only the NF-Y site is essential for the suppression by p53. Our study indicates that securin is a p53 target gene and may play a role in p53-mediated cellular response to DNA damage.
Zhou
Yunli
Y
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Mehta
Kshama R
KR
Choi
Andrew P
AP
Scolavino
Staci
S
Zhang
Xun
X
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001665:Binding Sites; D001761:Bleomycin / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins / Q000378:metabolism; D064249:Securin; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins; D064249:Securin; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; C578002:pituitary tumor-transforming protein 1, human; D001761:Bleomycin; D004317:Doxorubicin; D015739:Nocodazole