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Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Mutant p53 REs and the mechanism of gain of function in cancer

p53 functions as a sensor of cellular stress signals. A variety of stress signals stabilize its structure and bring about an increase in its concentration, with the end result of a variety of functional outcome preventing cancer. However, p53 itself is mutated in 50% of all cancer cases. p53 core domain is the main target for mutations in human tumors. 95% of the mutations identified in human tumors are found in this region. This underscores the importance of sequence-specific DNA binding by the core for p53 functions. Gain-of-function mutations are mutations that switch p53 into a tumor-promoting oncogene, by endowing the mutant protein with new abilities, activating new target genes, that can contribute to various stages of tumor progression. Multiple mechanisms were proposed to account for different mutant p53 gain-of-function activities. A major transcriptional mechanism for gain-of-function of mutant p53 is binding of mutant p53 through cooperation with other transcription factors. We will present a novel model for mutant p53 gain-of-function in cancer that reconciles many observations on the gain-of-function phenomenon. We will also present binding data demonstrating that the role played by DNA structure in mutant p53/DNA interaction follows the rules established for wild-type p53/DNA interactions.

Jessy Safieh
Demitrij Golovenko
Tali E. Haran

Faculty of Biology
Technion
Haifa, Israel

Phone: 972-4-8293767
Email: bitali@technion.ac.il