The document summarizes information about p53, a tumor suppressor protein. It discusses the history and discovery of p53, its structure and domains, mechanisms of stability and activation in response to stress. It also describes p53's key functions in cell cycle arrest and apoptosis. The document notes common mutations in p53 in different cancer types and potential therapeutic applications targeting p53 pathways.
2. INTRODUCTION
• Tumor Suppressor
• 53 kDa protein
• Encoded by TP53 gene
• Regulates cell cycle
3. HISTORY
• 1979 - David Lane and Lionel Crawford
• 1983 - The term “p53” was coined
• p53 acknowledged as an oncogene
• 1984 - David Wolf and Rotter
• 1989 - p53 tagged as a tumor suppressor
14. LUNG CANCER:
• 33% in adenocarcinomas to 70% in small cell lung
cancers
• GC to TA transversions
• Exogenous carcinogens such as benzopyrene
• Codons 157, 248 and 273
UV AND SKIN CANCERS:
• CC to TT transitions
• Codons 245 and 247/248
COLORECTAL CANCER:
• 34% proximal colon tumors
• 45% distal colon and rectal tumors
16. THERAPEUTIC APPLICATIONS
• Inhibiting interaction of MDM2 with p53
• Small molecule inhibitors: nutlins
• Antisense oligodeoxy nucleotides
• Inhibiting E6 protein of Human Papilloma Virus
• Leptomycin B and Actinomycin D
17. • Induction of apoptotic pathways
• Introduction of wt p53 gene into tumors
GENE THERAPY:
• 2004 - treatment of head and neck cancer in China
• McCormick and co-workers, USA - infection of the
tumor with recombinant adenovirus.