Structural biology of the tumor suppressor p53.
The tumor suppressor protein p53 induces or represses the expression of a variety of target genes involved in cell cycle control, senescence, and apoptosis in response to oncogenic or other cellular stress signals. It exerts its function as guardian of the genome through an intricate interplay of independently folded and intrinsically disordered functional domains. In this review, we provide insights into the structural complexity of p53, the molecular mechanisms of its inactivation in cancer, and therapeutic strategies for the pharmacological rescue of p53 function in tumors. p53 emerges as a paradigm for a more general understanding of the structural organization of modular proteins and the effects of disease-causing mutations.
Joerger
Andreas C
AC
Medical Research Council Centre for Protein Engineering, Cambridge, United Kingdom. acj2@mrc-lmb.cam.ac.uk
Fersht
Alan R
AR
D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D015195:Drug Design; D005799:Genes, Dominant; D016158:Genes, p53; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000502:physiology*
D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53