The p53 Family
The p53 tumor suppressor gene—the "guardian of the genome"—protects cells against genotoxic stress but is mutated in many cancers. It encodes one of a family of transcription factors (p53, p63, and p73) that regulate cell proliferation, differentiation, senescence, and cell death. Mutations in p53 allow cells to escape normal growth controls and thereby contribute to tumor malignancy.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology provides a comprehensive review of the functions of the p53 family. The contributors examine the normal roles of these transcription factors, the regulatory mechanisms that control p53 activity, and the part played by p53 mutations in tumorigenesis. They also discuss the evolution of the p53 family, which may originally have arisen to protect the integrity of the germ line. This collection also covers the structure of p53 and its isoforms, model systems for analyzing p53 function, studies of p53 polymorphisms, and therapeutic approaches aimed at targeting p53 defects in cancer.
1101420710
The p53 Family
The p53 tumor suppressor gene—the "guardian of the genome"—protects cells against genotoxic stress but is mutated in many cancers. It encodes one of a family of transcription factors (p53, p63, and p73) that regulate cell proliferation, differentiation, senescence, and cell death. Mutations in p53 allow cells to escape normal growth controls and thereby contribute to tumor malignancy.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology provides a comprehensive review of the functions of the p53 family. The contributors examine the normal roles of these transcription factors, the regulatory mechanisms that control p53 activity, and the part played by p53 mutations in tumorigenesis. They also discuss the evolution of the p53 family, which may originally have arisen to protect the integrity of the germ line. This collection also covers the structure of p53 and its isoforms, model systems for analyzing p53 function, studies of p53 polymorphisms, and therapeutic approaches aimed at targeting p53 defects in cancer.
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Overview

The p53 tumor suppressor gene—the "guardian of the genome"—protects cells against genotoxic stress but is mutated in many cancers. It encodes one of a family of transcription factors (p53, p63, and p73) that regulate cell proliferation, differentiation, senescence, and cell death. Mutations in p53 allow cells to escape normal growth controls and thereby contribute to tumor malignancy.

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology provides a comprehensive review of the functions of the p53 family. The contributors examine the normal roles of these transcription factors, the regulatory mechanisms that control p53 activity, and the part played by p53 mutations in tumorigenesis. They also discuss the evolution of the p53 family, which may originally have arisen to protect the integrity of the germ line. This collection also covers the structure of p53 and its isoforms, model systems for analyzing p53 function, studies of p53 polymorphisms, and therapeutic approaches aimed at targeting p53 defects in cancer.

Product Details

ISBN-13: 9780879698300
Publisher: Cold Spring Harbor Laboratory Press
Publication date: 06/22/2010
Pages: 360
Product dimensions: 7.30(w) x 10.20(h) x 0.90(d)

Table of Contents

Preface vii

The Origins and Evolution of the p53 Family of Genes Vladimir A. Belyi Prashanth Ak Elke Markert Haijian Wang Wenwei Hu Anna Puzio-Kuter Arnold J. Levine 1

The Tumor Suppressor p53: From Structures to Drug Discovery Andreas C. Joerger Alan R. Fersht 19

The Isoforms of the p53 Protein Marie P. Khoury Jean-Christophe Bourdon 39

p63 and p73, the Ancestors of p53 Volker Dötsch Francesca Bernassola Daniel Coutandin Elenora Candi Gerry Melino 49

Transcriptional Regulation by p53 Rachel Beckerman Carol Prives 63

Posttranslational Modification of p53: Cooperative Intergrators of Function David W. Meek Carl W. Anderson 81

The Regulation of the p53-mediated Stress Response by MDM2 and MDM4, 97 Mary Ellen Perry 97

Tied Up in Loops: Positive and Negative Autoregulation of p53 Xin Lu 109

TP53 Mutations in Human Cancers: Origins, Consequences, and Clinical Use Magali Olivier Monica Hollstein Pierre Hainaut 123

Clinical Outcomes and Correlates of TP53 Mutations and Cancer Ana I. Robles Curtis C. Harris 141

Single-nucleotide Polymorphisms in the p53 Signaling Pathway Lukasz F. Grochola Jorge Zeron-Medina Sophie Mériaux Gareth L. Bond 157

Tumor Suppressive Functions of p53 Jack T. Zilfou Scott W. Lowe 175

p53 Regulation of Metabolic Pathways Eyal Gottlieb Karen H. Vousden 187

p53 Regulation of the IGF-1/AKT/mTOR Pathways and the Endosomal Compartment Zhaohui Feng 199

The Role of p53 Gene Family in Reproduction Wenwei Hu 209

Using Mice to Examine p53 Functions in Cancer, Aging, and Longevity Lawrence A. Donehower 221

Mutant p53 Gain-of-Function in Cancer Moshe Oren Varda Rotter 239

Mouse Models of p53 Functions Guillermina Lozano 255

Zebrafish Models of p53 Functions Narie Y. Storer Leonard I. Zon 267

Phylogeny and Function of the Invertebrate p53 Superfamily Rachael Rutkowski Kay Hofmann Anton Gartner 279

p53-based Cancer Therapy David P. Lane Chit Fang Cheok Sonia Lain 293

Pathologies Associated with the p53 Response Andrei V. Gudkov Elena A. Komarova 317

p53 Research: The Past Thirty Years and the Next Thirty Years David Lane Arnold Levine 343

Index 353

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