p53 is a potent tumor suppressor. Its job is to scan along DNA, identify mutations that might cause cancer, and then halt cell growth until they can be repaired—it kills the cell if they cannot. It is mutated in approximately 50 percent of human tumors, and in its absence, DNA mutations can accrue while the cell divides, often forming a tumor. But some p53 mutants exhibit a nefarious “dominant negative” effect: when they are around, they prevent wild-type (normal) p53 molecules from working.
Because p53 works as a tetramer—a complex of four p53 molecules all bound together—it has generally been presumed that this dominant negative effect is achieved when mutant p53 molecules link up with normal counterparts to form nonfunctional tetramers. But new work reported in Nature Chemical Biology suggests that the process is more complex; some mutants can form much larger aggregates, not only with wild-type p53 but also with its related tumor suppressors p63 and p73. In addition to its blocking the function of these proteins, this aggregation can induce cellular changes that further contribute to tumorigenesis.
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