The tumor suppressor protein p53 is a transcription factor. p53 monomers assemble into tetramers that bind to consensus sequences in the DNA and activate the transcription of p53 response genes. P53 target genes are involved in the regulation of proliferation, apoptosis and genomic stability. The loss of p53 functions can promote the development and progression of malignant tumors. This can be based on various mechanisms. The loss of both TP53 alleles is observed in bone and soft tissue sarcomas. In many tumors the product of one allele is changed by a point mutation. Point-mutated monomers force wild-type monomers into an altered conformation. Such a dominant-negative mutation blocks DNA binding and transcription. After loss of the wild-type allele, mutant p53 monomers form tetramers that cannot bind to consensus sequences in the DNA. The MDM2 gene is amplified in about a third of soft tissue sarcomas. The encoded protein blocks the transactivation domains of p53 and mediates p53 ubiquitination and degradation in the proteasome. Ubiquitination and subsequent proteolysis of p53 can also be mediated by association with E6 proteins of the human papillomavirus.