Non-p53 p53RE binding protein, a human transcription factor functionally analogous to P53.
نویسندگان
چکیده
The transactivation activity of the p53 tumor suppressor protein is critical for regulating cell growth and apoptosis. We describe the identification of a transcription factor that is functionally similar to p53 and contains the same DNA binding and transcription activities specific for the p53 responsive DNA element (p53RE). This protein was highly purified through chromatography from HeLa cell extracts. The purified protein was able to bind specifically to the p53RE derived from a p21(waf1) promoter and to stimulate p53RE-dependent transcription but not basal transcription in vitro. Its DNA-binding activity was inhibited by the wild type but not mutant p53RE-containing DNA oligomers. Also, this p53RE-binding activity was found in human p53 null Saos-2 osteosarcoma and H1299 small cell lung carcinoma cells. Interestingly, this activity exhibited a p53RE sequence preference that was distinct from the p53 protein. The activity is neither p53 nor p73, because anti-p53 or anti-73 antibodies were unable to detect this purified protein nor were the antibodies able to alter the p53-like activity, the p53RE-protein complex. These results demonstrate that, besides p73, an additional p53-like protein exists in cells, which is named NBP for non-p53, p53RE binding protein.
منابع مشابه
The Role of Tumor Protein 53 Mutations in Common Human Cancers and Targeting the Murine Double Minute 2–P53 Interaction for Cancer Therapy
The gene TP53 (also known as protein 53 or tumor protein 53), encoding transcription factor P53, is mutated or deleted in half of human cancers, demonstrating the crucial role of P53 in tumor suppression. There are reports of nearly 250 independent germ line TP53 mutations in over 100 publications. The P53 protein has the structure of a transcription factor and, is made up of several domains. T...
متن کاملBCL6 is regulated by p53 through a response element frequently disrupted in B-cell non-Hodgkin lymphoma.
The BCL6 transcriptional repressor mediates survival, proliferation, and differentiation blockade of B cells during the germinal-center reaction and is frequently misregulated in B-cell non-Hodgkin lymphoma (BNHL). The p53 tumor-suppressor gene is central to tumorigenesis. Microarray analysis identified BCL6 as a primary target of p53. The BCL6 intron 1 contains a region in which 3 types of gen...
متن کاملInteractions of Chromatin Context, Binding Site Sequence Content, and Sequence Evolution in Stress-Induced p53 Occupancy and Transactivation
Cellular stresses activate the tumor suppressor p53 protein leading to selective binding to DNA response elements (REs) and gene transactivation from a large pool of potential p53 REs (p53REs). To elucidate how p53RE sequences and local chromatin context interact to affect p53 binding and gene transactivation, we mapped genome-wide binding localizations of p53 and H3K4me3 in untreated and doxor...
متن کاملMicrosoft Word - 28610168-file00.docx
Anthracyclines are effective genotoxic anticancer drugs for treating human malignancies; however, their clinical use is limited by tumour resistance and severe cardiotoxicity (e.g. congestive heart failure). Epirubicin (EPI) is less cardiotoxic compared to other canonical anthracyclines (e.g, doxorubicin). This has been attributed to its unique glucuronidation detoxification pathway. EPI is pri...
متن کاملEpirubicin upregulates UDP glucuronosyltransferase 2B7 expression in liver cancer cells via the p53 pathway.
Anthracyclines are effective genotoxic anticancer drugs for treating human malignancies; however, their clinical use is limited by tumor resistance and severe cardiotoxicity (e.g., congestive heart failure). Epirubicin (EPI) is less cardiotoxic compared with other canonical anthracyclines (e.g., doxorubicin). This has been attributed to its unique glucuronidation detoxification pathway. EPI is ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 95 12 شماره
صفحات -
تاریخ انتشار 1998