p53 and Cancer Karina Espinoza Biochemistry 118Q What is p53 A protein found inside cells A stress sensor of signals DNA damage hypoxia oncogene expression nutrient deprivation ribosome dysfunction In unstressed cells p53 is inactive MDM2 ubiquitin ligase degradation of p53 Today s focus stressor DNA damage p53 senses damaged DNA aids in regulation of DNA repair p53 tumor suppressor protein prevents cancer What is a tumor a mass of tissues that result from excessive uncontrolled cell division can be benign or malignant What does p53 do p53 has 2 main functions 1 Cell cycle arrest p53 STOPS cell cycle until DNA is repaired Is DNA damaged Is DNA damaged 2 Apoptosis cell suicide p53 transcription factor for 3 pro apoptotic genes Cytochrome c release Caspase activation cleavage of key cell proteins that cause cell death Cancer and p53 p53 prevents cancer evidence knockout mice Inheriting only 1 copy of functional p53 gene predisposition to cancer many kinds Li Fraumeni syndrome Patients have a 50 chance of developing cancer by 30 yrs old rare condition Is this the only way that p53 relates to cancer p53 is the most commonly mutated gene in cancer P53 has been found to be mutated in more than 52 kinds of cancers How does a mutation in p53 cancer What is Cancer Uncontrolled growth proliferation of cells Mutant p53 can NO longer bind to DNA in an effective way p21 protein is not made no stop signal for cell division no apoptosis arrest Even if DNA is damaged cell proliferates mutations propagate malignant tumors are formed cancer With p53 Without p53 Propagation of mutations p53 p53 Cell G1 arrested cell DNA repair Failed G1 arrest p53 Cell Additional mutations Malignant cell Using what we know about p53 cancer therapy Cancers that have a p53 mutation poor prognosis Why Tumor cells not likely to undergo apoptosis cell cycle arrest when damaged by therapy Radiation and chemotherapy may secondary cancers Alternative Treatments Gene Therapy Introducing genetic material into cells to compensate for abnormal genes or to make beneficial protein Gene Therapy Gendicine China 2003 What is Gendicine Recombinant Human Ad p53 Injection Target cells cancer cells has been FDA approved for neck and head sarcomas Vector replication defective adenovirus Viruses can infect specific cells and deliver their DNA Genetically engineered virus to have p53 gene p53 will be expressed via the host s transcription and translation processes Results cancer cured apoptosis of damaged cells References www ncbi nlm nih gov disease GIFS p53 gif https docs google com viewer a v pid gmail attid 0 1 1 thid 12e6af9cde31279f mt application pdf url https mail google com mail ui 3D2 26ik 3D2291030fe1 26view 3Datt 26th 3D12e6af9cde31279f 26attid 3D0 1 1 26disp 3Dattd 26zw sig AHIEtbT3A1JxdjhKvpMHewHumj0hmd6tg http www ncbi nlm nih gov omim 191170 http www nejm org doi full 10 1056 NEJM199205143262008 https docs google com viewer a v pid gmail attid 0 1 thid 12e8dabeb5fd7ab7 mt application pdf url https mail google com mail ui 3D2 26ik 3D2291030fe1 26view 3Datt 26th 3D12e8dabeb5fd7ab7 26attid 3D0 1 26disp 3Dattd 26realattid 3Df gkyn2qf00 26zw sig AHIEtbQQKGdMULMkRPotUaKcYTPwg m5kww http www nejm org doi full 10 1056 NEJMcibr041288 http jnci oxfordjournals org content 88 20 1442 full pdf html
View Full Document
Unlocking...