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TCP80 and RHA are positive p53 IRES trans‐acting factors poorly expressed in cancer cells with defective p53 response to DNA damage
Author(s) -
Yang DaQing,
Halaby MarieJo,
Jiang Hong,
Miskimins W. Keith
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.710.6
Subject(s) - internal ribosome entry site , dna damage , translation (biology) , biology , cancer cell , oncogene , messenger rna , microbiology and biotechnology , cancer research , dna , cancer , cell cycle , gene , genetics
This project studies translational regulation of p53 in breast cancer. The tumor suppressor p53 is essential for the protection of cells against tumorigenic transformation. p53 protein accumulates in the cell following stressful events such as DNA damage. Induction of p53 is known to be regulated at the level of translation. We previously discovered that an internal ribosome entry site (IRES) is located at the 5′‐UTR of the p53 mRNA which controls cap‐independent translation of p53 following DNA damage (Yang, et al, Oncogene, 2006; Halaby and Yang, Gene, 2007). We have recently identified two p53 IRES‐trans activating factors (ITAFs), TCP80 and RHA, that positively regulate p53 IRES activity in response to DNA damage. Both TCP80 and RHA are involved in protein translation and ribosome biogenesis. We further show that two breast cancer cell lines, known to harbor wild‐type p53, have defective p53 induction and diminished p53 IRES activity following DNA damage. Moreover, the expression levels of TCP80 and RHA are extremely low in these cells. A significant increase in p53 IRES activity was observed only when TCP80 and RHA were co‐expressed in these two cell lines. Our results suggest that these two positive p53 ITAFs are important for p53 induction following DNA damage and their defective expression may be related to the development of breast cancer. This project is supported by an IDEA Award from the Department of Defense.