Tumour suppression by p53: the importance of apoptosis and cellular senescence.
p53 is regarded as a central player in tumour suppression, as it controls programmed cell death (apoptosis) as well as cellular senescence. While apoptosis eliminates cells at high risk for oncogenic transformation, senescence acts as a barrier to tumourigenesis by imposing irreversible cell cycle arrest. p53 can act directly or indirectly at multiple levels of the tumour suppression network by invoking a myriad of mechanisms. p53 induces the extrinsic and intrinsic apoptotic pathways at multiple steps to ensure an efficient death response. This response involves transcriptional activation or repression of target genes, as well as the recently identified microRNAs, and transcription-independent functions. Importantly, p53 loss of function is required for tumour maintenance. Therefore, therapeutic strategies aimed at reactivation of p53 in tumours emerge as a promising approach for the treatment of cancer patients.
Zuckerman
Valentina
V
Lautenberg Centre for General and Tumour Immunology, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
Wolyniec
Kamil
K
Sionov
Ronit V
RV
Haupt
Sue
S
Haupt
Ygal
Y
D017209:Apoptosis; D016922:Cellular Senescence; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D004268:DNA-Binding Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; D020033:Protein Isoforms; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins