© 2020 • 358 pages, illustrated (53 color and 3 B&W), index
Hardcover • $75.00 • ISBN 978-1-621823-44-5

The PTEN protein is a phosphatase that plays important roles as a tumor suppressor by negatively regulating the PI3K/Akt signaling pathway that controls cell proliferation and survival. Impaired PTEN function leads to unrestrained downstream signaling and, in turn, uncontrolled cell growth and cancer. PTEN also has other roles: Recent work has implicated it in a variety of additional biological processes, including control of DNA replication and repair, and in disparate pathological conditions (e.g., autism).

Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine covers all aspects of PTEN biology and its roles in human diseases. The contributors discuss the structural characteristics of PTEN; its functions at the plasma membrane as well as in the cytoplasm and nucleus; the mutations, interacting partners, and posttranslational modifications that affect its expression levels, subcellular localization, and enzymatic activity; and how this activity ultimately leads to changes in cell growth, migration, and morphology, as well as in gene expression, chromatin dynamics, and the maintenance of genomic stability. A historical perspective that covers the initial discovery and subsequent characterization of PTEN is also included.

In addition, the authors discuss the loss of PTEN function in various cancers, as well as in immune, metabolic, and neurological disorders (e.g., autoimmunity, type 2 diabetes, and autism), and consider how this knowledge can be exploited for diagnostic and therapeutic purposes. This volume is therefore essential reading for all cell and molecular biologists, cancer biologists, and pharmacologists interested in PTEN’s remarkable biological complexity and importance in human health.

Preface

HISTORICAL PERSPECTIVE

Discovery of the PTEN Tumor Suppressor and Its Connection to the PI3K and AKT Oncogenes

Ramon Parsons

SECTION 1: STRUCTURE AND FUNCTION

Structural Mechanisms of PTEN Regulation

Glenn R. Masson and Roger L. Williams

Dual-Specific Protein and Lipid Phosphatase PTEN and Its Biological Functions

Taojian Tu, Jingyu Chen, Lulu Chen, and Bangyan L. Stiles

Posttranslational Regulation and Conformational Plasticity of PTEN

Larissa Kotelevets, Barbara Trifault, Eric Chastre, and Mark G.H. Scott

The Impact of Genetic Variants on PTEN Molecular Functions and Cellular Phenotypes

Nicholas Hasle, Kenneth A. Matreyek, and Douglas M. Fowler

SECTION 2: REGULATION

PTEN Nuclear Functions

Jason Ho, Edward S. Cruise, Ryan J.O. Dowling, and Vuk Stambolic

The Complex Landscape of PTEN mRNA Regulation

Erin Sellars, Martino Gabra, and Leonardo Salmena

PTEN Mouse Models of Cancer Initiation and Progression

Yu-Ru Lee and Pier Paolo Pandolfi

SECTION 3: SIGNALING PATHWAYS

PTEN as a Guardian of the Genome: Pathways and Targets

Xinyi Fan, Jeffrey Kraynak, Jonathan P.S. Knisely, Silvia C. Formenti, and Wen H. Shen

PTEN: Bridging Endocytosis and Signaling

Matthew F. Lee and Lloyd C. Trotman

PTEN in Chromatin Remodeling

Jingyi Yang and Yuxin Yin

SECTION 4: PTEN AND HUMAN DISEASE

PTEN in Hereditary and Sporadic Cancer

Joanne Ngeow and Charis Eng

PTEN in Regulating Hematopoiesis and Leukemogenesis

Yilin Wu, Haichuan Zhu, and Hong Wu

PTEN in the Stroma

Katie A. Thies, Julia E. Lefler, Gustavo Leone, and Michael C. Ostrowski

Autism Spectrum Disorder Associated with Germline Heterozygous PTEN Mutations

Thomas W. Frazier

Connecting Genotype with Behavioral Phenotype in Mouse Models of Autism Associated with PTEN Mutations

Amy E. Clipperton-Allen and Damon T. Page

PTEN in Autism and Neurodevelopmental Disorders

Sebastian Rademacher and Britta J. Eickholt

Metabolic Role of PTEN in Insulin Signaling and Resistance

Yu Zhe Li, Antonio Di Cristofano, and Minna Woo

The Role of PTEN in Innate and Adaptive Immunity

Henry Taylor, Arian D.J. Laurence, and Holm H. Uhlig

Toward Systems Pathology for PTEN Diagnostics

Nahal Haddadi, Glena Travis, Najah T. Nassif, Ann M. Simpson, and Deborah J. Marsh

Precise Immunodetection of PTEN Protein in Human Neoplasia

Rafael Pulido, Janire Mingo, Ayman Gaafar, Caroline E. Nunes-Xavier, Sandra Luna, Leire Torices, Javier C. Angulo, and José I. López

Index