We conclude that Fbxw7 is an important regulator of skin tumor progression, and that a partial germline deficiency causes increased susceptibility to papilloma development, particularly in the context of a reduced gene dosage for p53. These data extend and support the conclusion above that Fbxw7 is an important tumor suppressor gene that interacts strongly with the p53 pathway. This evidence concerns the gene TP53 and skin neoplasm.