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Significance Mice that have homozygous deletion of the p53 tumor suppressor protein universally die of malignancy, generally before 6 months of age. We show that hemizygous deficiency of RALBP1 (RLIP76 or Rlip) confers a degree of protection from spontaneous malignancy that has never previously been observed. This discovery introduces a paradigm for p53 function, in which Rlip plays a central role as an effector that appears necessary for the cancer susceptibility of p53 null mice. Because p53 loss has a powerful effect on genomic instability that contributes to the initiation and promotion of cancers and to drug and radiation resistance in humans, our findings provide a method for prevention and therapy of p53-deficient cancer.

Rlip depletion prevents spontaneous neoplasia in TP53 null mice