Fig. 2: Codon 72 polymorphisms as modulators of p53-mediated responses: In response to DNA damage, the R72 variant is more effective at inducing apoptosis, whereas P72 is more effective at mediating cell cycle arrest and repair. | Cell Death & Differentiation

Fig. 2: Codon 72 polymorphisms as modulators of p53-mediated responses: In response to DNA damage, the R72 variant is more effective at inducing apoptosis, whereas P72 is more effective at mediating cell cycle arrest and repair.

From: Exploring the genetic and molecular basis of differences in multiple myeloma of individuals of African and European descent

Fig. 2

As a result, each variant may respond to different selection pressures, depending upon cell and tissue context. In the context of MGUS- > MM progression, the R72 variant is more effective than P72 at eliminating single cells with excess/abnormal recombination, thus preventing the occurrence of initiating oncogenic translocations that cause MGUS. This effect is fully eliminated by TP53 mutation. In the context of epithelial cancers (breast; colon), the P72 variant is more effective than R72 at repressing cell proliferation across the tissue therefore impairing physiologic competence in the face of persistent mutagenic exposure. This effect is fully eliminated by TP53 mutation that enables surviving initiated tumor cells to progress towards aggressive cancer.

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