Protein Prenylation, Part B - 1st Edition - ISBN: 9780124159228, 9780124159648

Protein Prenylation, Part B, Volume 30

1st Edition

Serial Volume Editors: Christine Hrycyna Martin Bergo Fuyuhiko Tamanoi
eBook ISBN: 9780124159648
Hardcover ISBN: 9780124159228
Imprint: Academic Press
Published Date: 28th November 2011
Page Count: 372
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Table of Contents

Preface

The Enzymology of CAAX Protein Prenylation

I. Abstract

II. Introduction

III. Protein FTase

IV. Protein GGTase-I

V. Conclusions

Acknowledgments

CAAX Processing and Yeast a-Factor Biogenesis

I. Abstract

II. Introduction

III. The a-Factor Mating Pheromone of S. cerevisiae as an Early Prototype for Dissecting the CAAX-Processing Pathway

IV. Biogenesis Pathway of a-Factor: Genetic and Biochemical Analysis of the a-Factor Machinery

V. Progeria—The Role of Prenylation and ZMPSTE24 in Progeroid Disorders

VI. A Prenylated, Secreted Molecule Involved in Drosophila Germ Cell Migration Requires a Pathway Strikingly Similar to That of a-Factor Biogenesis

Acknowledgments

Prenylation and Phosphorylation of Ras Superfamily Small GTPases

I. Abstract

II. Introduction

III. Small GTPase Prenylation

IV. C-Terminal Phosphorylation of Prenylated Ras Family Small GTPases

V. C-Terminal Phosphorylation of Prenylated Rho Family Small GTPases

VI. C-Terminal Phosphorylation of Prenylated Rab Family Small GTPases

VII. Conclusions

Acknowledgments

Biochemical and Biological Functions of Isoprenylcysteine Carboxyl Methyltransferase

I. Abstract

II. Introduction

III. Icmt: Structure and Biological Function

IV. ICMT Substrate Specificity

V. Effect of Methylation by Icmt on Substrate Function: In Vitro Studies

VI. ICMT Effect on Substrate Function: In Vivo Studies

VII. Conclusions

Chemical Probes of Protein Prenylation

I. Abstract

II. Introduction

III. Prenyl Analogs as FTase Inhibitors (FTIs)

IV. Prenyl Analogs as Mechanistic and Structural Probes

V. Substrate Specificity Studies

VI. Prenyl Proteomics Studies

VII. Future Directions

Geranylgeranyltransferase-1 Inhibitors

I. Abstract

II. Introduction

III. Biochemistry of Protein Prenylation

IV. Validation of GGT-1 as a Target in a Genetic Mouse Model

V. Design of CaaX Peptidomimetics as PTIs and Identification of PTIs from High-Throughput Screens (HTS)

VI. FTIs as Anticancer Drugs

VII. GGTI Effects in Cultured Cells and In Vivo

VIII. GGTIs in the Clinic

IX. The Use of PTIs in Other Diseases

X. Future Directions and Challenges

Acknowledgments

Small-Molecule Inhibitors of GGTase-I from the Heterocycle Library Derived from Phosphine Catalysis

I. Abstract

II. Introduction

III. Phosphine Catalysis-Based Chemical Compound Library and Identification of Initial GGTI Compounds P3-E5 and P5-H6

IV. Cell Active Compound P61-A6

V. Tumor Growth Inhibition by P61-A6

VI. Long Plasma Half Life of P61-A6 and Pharmacokinetic Parameters

VII. Identification of Dual Specificity Inhibitors of GGTase-I and RabGGTase

VIII. Identification of Specific Inhibitors of RabGGTase from the Library

IX. Conclusion and Future Prospects

Acknowledgment

Inhibition of Rab Prenylation

I. Abstract

II. Introduction

III. RabGGTase Inhibitors

IV. Summary and Outlook

Inhibitors of Postprenylation CAAX Processing Enzymes

I. Abstract

II. Introduction

III. Inhibitors of Rce1

IV. Inhibitors of Icmt

V. Conclusion

The Ras Converting Enzyme (Rce1p)

I. Abstract

II. Introduction

III. Identification of Rce1p and Its Orthologs

IV. The Basis for Rce1p as a Therapeutic Target for Disease

V. Rce1p and Ste24p Have Different Target Specificities

VI. The Recognition of Specific CaaX Motifs is Influenced by Protein Context

VII. Rce1p Influences the Localization of Some But Not All of Its Targets

VIII. Rce1p Inhibitors Can Be Assay Independent and Assay Dependent

IX. Structural Chemistry and Proposed Mechanism

X. Conclusions and Future Directions

Acknowledgments

Cysmethynil, a Specific Small-Molecule Inhibitor of Isoprenylcysteine Carboxylmethyl Transferase (Icmt)

I. Abstract

II. Prenylation Process

III. Rationale for Targeting Icmt

IV. Icmt and Its Functional Importance in Biology

V. Development of Icmt Inhibitors

VI. Cysmethynil, a Nonstructure Analog Small-Molecule Inhibitor of Icmt

VII. Inhibition of Icmt by Cysmethynil Induces Autophagy and Cell Death, Potential for Cancer Therapy

VIII. Cysmethynil Inhibition of Icmt Results in Reduction of Rho-Mediated Cell Migration, Suggesting a Potential Role in Cancer Metastasis

IX. Current and Future Work to Identify Better Icmt Inhibitors Through Medicinal Chemistry

The Isoprenoid Biosynthetic Pathway and Statins

I. Abstract

II. The Isoprenoid Biosynthetic Pathway

III. Statins

IV. Statins and the IBP

V. Future Directions

Inhibition of Farnesyl and Geranylgeranyl Diphosphate Synthases

I. Abstract

II. The Isoprenoid Biosynthetic Pathway

III. Nitrogenous Bisphosphonates

IV. GGDPS Inhibitors

V. Future Directions


Description

This volume of The Enzymes features high-caliber thematic articles on the topic of glycosylphosphatidylinositol (GPI) anchoring of proteins.

Key Features

  • Contributions from leading authorities
  • Informs and updates on all the latest developments in the field

Readership

Biochemists, cell biologists, molecular biologists, biophysicists


Details

No. of pages:
372
Language:
English
Copyright:
© Academic Press 2011
Published:
Imprint:
Academic Press
eBook ISBN:
9780124159648
Hardcover ISBN:
9780124159228

About the Serial Volume Editors

Christine Hrycyna Serial Volume Editor

Affiliations and Expertise

Purdue University, West Lafayette, Indiana

Martin Bergo Serial Volume Editor

Affiliations and Expertise

Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Hospital, Gothenburg, Sweden

Fuyuhiko Tamanoi Serial Volume Editor

Fuyu Tamanoi is a biochemist who has served on the UCLA School of Medicine and UCLA College faculty since he joined the Department of Microbiology, Immunology & Molecular Genetics in 1993. He became a full professor in 1997. Since 1996, he has been a Director of Signal Transduction Program Area at Jonsson Comprehensive Cancer Center. Dr. Tamanoi earned his B.S. and M.S. in Biochemistry at the University of Tokyo. He received PhD in Molecular Biology at Nagoya University in 1977. He was a postdoctoral fellow at Harvard Medical School, where he worked on bacteriophage DNA replication. From 1980 to 1985, he was a senior staff investigator at Cold Spring Harbor Laboratory, where he worked on adenovirus DNA replication. From 1985 to 1993, he was an Assistant Professor and then Associate Professor at the University of Chicago, where he initiated studies on lipid modification of the Ras family proteins. His laboratory research centers on signal transduction and signal transduction inhibitors. He is currently exploring ways to deliver signal transduction inhibitors using nanoparticles.

Affiliations and Expertise

Professor and Vice Chair, Dept. of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, USA Director, Signal Transduction Program Area, Jonsson Comprehensive Cancer Center, USA