Targeting Ribosome Assembly Factors Selectively Protects p53 Positive Cells from Chemotherapeutic Agents
Molecular Biology of the Cell
2017 ASCB Annual Meeting
Many chemotherapeutic agents act in a nondiscriminatory fashion, targeting both cancerous and noncancerous cells in Sphase and Mphase. One approach to reduce the toxic side effects in normal tissue is to exploit the differences in p53 functionality between cancerous and noncancerous cells. For example, activating p53 signaling by nongenotoxic means can transiently arrest noncancerous p53 positive cells in G1 phase and protect them from the cytotoxic effects of chemotherapeutic drugs. However, since most cancerous cells have faulty p53 signaling, they will proceed to cycle, and continue to be affected by the drug. In this study we asked if this G1‐phase arrest and cytoprotection can be achieved by targeting ribosome biogenesis. Through the expression of a dominant negative mutant ribosome assembly factor Bop1, we were able to transiently inhibit rRNA maturation. Using this genetic model, we have shown that inhibition of rRNA maturation protects 3T3 cells from chemotherapeutic agents camptothecin and methotrexate.
Sapio RT, Nezdyur AN, Krevetski M, Anikin L, Manna VJ, Minkovsky N, Pestov D. Targeting ribosome assembly factors selectively protects p53 positive cells from chemotherapeutic agents [Conference Abstract P1305]. Molecular Biology of the Cell. 2017 Dec 15;28(26):3727. doi: 10.1091/mbc.E17-10-0618. PMID: 29237772. PMCID: PMC5739290.
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The complete published abstracts for this conference are available as "Supplemental Materials" at https://www.molbiolcell.org/doi/10.1091/mbc.e17-10-0618