This book provides the readers with an overview of research on p53, which has been shown to play a role in numerous crucial biological pathways in normal and cancer cells. Leading scientist in the field, who have all made direct contributions to the understanding of the molecular events underpinning p53 function, have been invited to contribute the various chapters, which discuss the current knowledge of the signaling cascades that are activated by mutations in p53 and overexpression of MDM2, frequently found in human cancer, and are major causes of oncogenesis.

This book features chapters on the molecular basis of oncogenesis induced by gain of function mutation of p53, signaling pathways induced by MDM2 overexpression, control of mutant or wild-type p53 function by MDM2 and MDMX, p53 mutation in hereditary cancer, and structural aspects that activate mutant p53 which can be targeted by drug therapy. This book should be useful for scientists at all levels.

Inhalt

p53 and hereditary cancer.- Alterations of p63 and p73 in human cancers.- Cooperation of p53 mutations with other oncogenic alterations in cancer.- p53 mutations and how mutations affect transcription.- Transcriptional regulation by mutant p53 and oncogenesis.- p53 mutation in the genesis of metastasis.- Structural studies on mechanisms to activate mutant p53.- Mutant p53 and the response to chemotherapy and radiation.- The p53-MDM2 loop: a critical juncture of stress response.- Mechanisms of mutant p53 stabilization in cancer.- Crosstalk between Mdm2, p53 and HIF-1: distinct responses to oxygen stress and implications for tumour hypoxia.- MDM2 overexpression, activation of signaling networks, and cell proliferation.- p53-independent effects of MDM2.- Splice variants of MDM2 in oncogenesis.- MDM2 and MDMX involvement in human cancer.- Targeting the p53-MDM2- MDMX loop for cancer therapy.- Involvement of p53 in the repair of DNA double strand breaks: Multifaceted roles of p53 in homologous recombination repair (HRR) and non-homologous end joining (NHEJ).- The role of tumor suppressor p53 in the antioxidant defense and metabolism.- Lung cancer stem cells, p53 mutations and MDM2.