Protein Prenylation, Part A

Preface

Protein Prenylation

I. Abstract

II. Steps in the Trail of Research

Insights into the Function of Prenylation from Nuclear Lamin Farnesylation

I. Abstract

II. Introduction

III. Subcellullar Trafficking and Processing of Prelamin A

IV. Step 2 Endoprotease Activity and Zmpste24

V. Functional Aspects of Lamin Farnesylation

VI. Relationship of Lamin Prenylation to the Functional Role of Prenylation in Other Proteins

Posttranslational Processing of Nuclear Lamins

I. Abstract

II. Introduction

III. B-Type Lamins

IV. A-Type Lamins

V. Defects in Prelamin A Processing and Disease

VI. Alternate Prenylation of Prelamin A

VII. The Purpose of Prelamin A Processing

VIII. Concluding Thoughts

Acknowledgments

Prenylated Proteins in Peroxisome Biogenesis

I. Abstract

II. Peroxisomes

III. Biogenesis of Peroxisomes

Lipid Modification of Ras Superfamily GTPases

I. Abstract

II. Introduction

III. Ras Superfamily Prenyltransferases

IV. Ras Family Members

V. Rho Family Members

VI. Rab Family Members

VII. The Arf Family of Small GTPases

VIII. The Ran Small GTPase

IX. Prenyltransferases as Therapeutic Targets

X. Conclusion

Acknowledgments

Heterogeneous Prenyl Processing of the Heterotrimeric G protein Gamma Subunits

I. Abstract

II. Heterotrimeric G Proteins and Prenylation of the Gγ Subunit

III. Functional Role of G Protein γ Subunit Prenylation

IV. Variation in Prenyl Processing of Brain G Proteins

V. Conclusion

Farnesylation Versus Geranylgeranylation in G-Protein-Mediated Light Signaling

I. Abstract

II. Introduction

III. Characteristic Properties of Phototransduction in Retinal Rod Cells

IV. Particular Lipidation of Photoreceptor Proteins

V. Biochemical Differences Between Farnesylation and Geranylgeranylation

VI. Physiological Significance of Farnesylation of Gtγ

VII. Biological Significance and Conclusion

Organization and Function of the Rab Prenylation and Recycling Machinery

I. Abstract

II. Rab GTPases

III. Pathways of Rab Prenylation

IV. Organization of the Rab Prenylation Complex and Mechanism of the Prenylation Reaction

V. Structure of the Rab:GDI Complex and Its Functional Segregation from Rab:REP Complex

VI. Extraction of Rab Proteins from Membranes by GDI and REP

VII. Targeting of Rabs to Specific Membranes

VIII. Rab Prenylation in Disease

IX. Conclusions

Protein Prenylation CaaX Processing in Plants

I. Abstract

II. The Plant Protein Prenyltransferase Enzymes

III. FT and GGT-I Substrates in Plants

IV. Protein Prenylation—A Crossroad Between Signaling and Metabolism

V. Prenyltransferase Mutants in Plants

VI. CaaX Processing

VII. Summary

Acknowledgments

Posttranslational Isoprenylation of Tryptophan Residues in Bacillus subtilis

I. Abstract

II. Quorum Sensing in Bacteria

III. Genetic Competence in B. subtilis

IV. Primary Gene Cluster for ComX Pheromone Production

V. Posttranslational Modification of ComX Pheromone

VI. Structure–Activity Relationships of ComXRO-E-2 Pheromone

VII. Is Posttranslational Isoprenylation of Tryptophan Universal?

VIII. Summary and Future Prospects

Acknowledgment

Global Analysis of Prenylated Proteins by the Use of a Tagging via Substrate Approach

I. Abstract

II. Introduction

III. General Approach: Tagging via Substrate Approach Utilizing Azide Chemistry

IV. Detection of Farnesylated Proteins

V. Detection of Geranylgeranylated Proteins

VI. Overall Profiles of Farnesylated and Geranylgeranylated Proteins and Further Improvements

VII. Applications of the TAS Methods

VIII. Other Tagging Methods and Toward Constructing Prenylome

Acknowledgment

Global Identification of Protein Prenyltransferase Substrates

I. Abstract

II. Introduction

III. Methods for Discovering and Predicting Prenyltransferase Substrates

IV. Prenylation in Pathogenic Organisms: Structural and Biochemical Insights

V. Conclusions

Acknowledgments

Structural Biochemistry of CaaX Protein Prenyltransferases

I. Abstract

II. Protein Farnesyltransferase Structure and Reaction Cycle

III. Protein Geranylgeranyltransferase-I Structure and Reaction Cycle

IV. Determinants of Ca1a2X Substrate Selection in FTase and GGTase-I

V. Structure of Candida albicans Protein Geranylgeranyltransferase-I

VI. Inhibitors of Protein Prenyltransferases as Cancer Chemotherapeutics

VII. FTase Inhibitors for Treatment of Malaria and Other Infectious Diseases

Genetic Analyses of the CAAX Protein Prenyltransferases in Mice

I. Abstract

II. Introduction

III. The Prenyltransferases FTase and GGTase-I

IV. FTase

V. GGTase-I

VI. Simultaneous Inactivation of FTase and GGTase-I

VII. Concluding Remarks

Farnesyl Transferase Inhibitors

I. Abstract

II. Targeting Ras with Farnesyl Transferase Inhibitors

III. Discovery of Farnesyl Transferase Inhibitors

IV. Activity of FTIs in Preclinical Cancer Models and Alternative Prenylation of Ras

V. Impact of FTIs on Other Farnesylated Proteins

VI. Clinical Studies of FTIs in Cancer

VII. Hutchinson–Gilford Progeria Syndrome: A Disease of Farnesylation?

VIII. Conclusions and Other Therapeutic Opportunities for FTIs

Acknowledgments