Protein Prenylation: Part A

Copyright
......Page 4
Contents......Page 6
Preface
......Page 12
Abstract......Page 15
Steps in the Trail of Research......Page 16
References......Page 17
Abstract......Page 19
Discovery of Lamin Farnesylation......Page 20
Subcellullar Trafficking and Processing of Prelamin A......Page 22
Step 2 Endoprotease Activity and Zmpste24......Page 24
Functional Aspects of Lamin Farnesylation......Page 26
Relationship of Lamin Prenylation to the Functional Role of Prenylation in Other Proteins......Page 28
References......Page 29
Abstract......Page 35
Protein Farnesyltransferase Structure and Reaction Cycle......Page 36
B-Type Lamins......Page 37
A-Type Lamins......Page 39
Defects in Prelamin A Processing and Disease......Page 41
Alternate Prenylation of Prelamin A......Page 46
The Purpose of Prelamin A Processing......Page 47
Concluding Thoughts......Page 48
References......Page 50
Peroxisomes......Page 57
Ras Superfamily Prenyltransferases......Page 58
Identification of Substrates One by One......Page 59
Detection of Geranylgeranylated Proteins......Page 213
Activity in Animal Models of Cancer......Page 261
Binding Partners of Pex19p......Page 63
Role of Pex19p in the Topogenesis of PMPs......Page 64
Rho GTPases on Peroxisomes......Page 65
References......Page 242
Abstract......Page 73
Introduction......Page 74
Farnesylation of Transducin gamma Subunit......Page 143
Farnesylation of H-Ras, N-Ras, K-Ras4A, and K-Ras4B......Page 83
Geranylgeranylation of RalA and RalB......Page 85
Farnesylation of Rheb1 and Rheb2......Page 86
Nonprenylated Ras Family Proteins......Page 87
Geranylgeranylation of Rho, Rac, and Cdc42 Proteins......Page 88
Prenylation of Other Rho Subfamily Members......Page 91
Rab Family Members......Page 92
The Arf Family of Small GTPases......Page 93
Clinical Evaluation of FTIs......Page 94
Conclusion......Page 97
References......Page 98
Abstract......Page 111
Quorum Sensing in Bacteria......Page 198
G Protein Structure and Signaling Dynamics......Page 112
Ggamma Subunit Diversity and Prenylation......Page 113
Membrane Attachment of Prenylated Proteins......Page 114
Reversible Trafficking Between Plasma Membranes and Endomembranes......Page 116
Protein-Protein Interactions......Page 117
Variation in Prenyl Processing of Brain G Proteins......Page 118
Unprenylated C-Terminus......Page 121
Unmethylated Ggamma......Page 122
Hematologic Malignancies......Page 302
Protein Prenylation-A Crossroad Between Signaling and Metabolism......Page 185
Ggamma Subunits not Processed by Rce1......Page 124
Sequence Determinants for the Altered Prenyl Processing of Ggamma5......Page 125
Functional Role of Unprocessed CaaX Sequences......Page 128
Conclusion......Page 129
References......Page 130
Abstract......Page 139
Introduction......Page 140
Characteristic Properties of Phototransduction in Retinal Rod Cells......Page 141
Biochemical Differences Between Farnesylation and Geranylgeranylation......Page 145
Rab Prenylation in Disease......Page 172
Generation and Molecular Characterization of S74L Knockin Mice......Page 146
Computational Work......Page 147
Farnesylation Essential for Light-Dependent Translocation of Transducin......Page 151
Lipid Hydrophobicity Determines the Intracellular Dynamics of Transducin......Page 153
Biological Significance and Conclusion......Page 155
References......Page 156
Organization and Function of the Rab Prenylation and Recycling Machinery......Page 161
Abstract......Page 249
The Prenyltransferases FTase and GGTase-I......Page 162
Organization of the Rab Prenylation Complex and Mechanism of the Prenylation Reaction......Page 164
Structure of the Rab:GDI Complex and Its Functional Segregation from Rab:REP Complex......Page 167
Simultaneous Inactivation of FTase and GGTase-I......Page 168
FT and GGT-I Substrates in Plants......Page 180
Small GTPase Substrates of FTase......Page 298
References......Page 174
Abstract......Page 177
Biochemical and Molecular Properties of the Plant FT and GGT-I......Page 178
The Plant GGT-I......Page 179
Other Small Molecule Prenyltransferase Inhibitors......Page 262
MUBs......Page 181
ROP/RAC GTPases......Page 182
Prenyl Group Type Affect on Protein Function......Page 184
The Arabidopsis FT beta-Subunit Mutant era1......Page 186
The ggt-Ib and FT/GGT-I α Subunit Mutants......Page 187
STE24......Page 188
RCE1......Page 189
ICMT......Page 190
Summary......Page 191
References......Page 192
Abstract......Page 197
Primary Gene Cluster for ComX Pheromone Production......Page 199
In Vitro Activity......Page 294
Structure-Activity Relationships of ComXRO-E-2 Pheromone......Page 202
Is Posttranslational Isoprenylation of Tryptophan Universal?......Page 204
Summary and Future Prospects......Page 205
References......Page 206
Global Analysis of Prenylated Proteins by the Use of a Tagging via Substrate Approach......Page 209
Abstract......Page 289
Introduction......Page 210
Detection of Farnesylated Proteins......Page 211
Applications of the TAS Methods......Page 215
Other Tagging Methods and Toward Constructing Prenylome......Page 216
References......Page 219
Abstract......Page 221
Introduction......Page 222
FPP and GGPP Analogs: Aiding in Prenyl Group Detection......Page 225
Structural Studies......Page 228
Peptide Library Studies: A High-Throughput Method of Identifying Potential Prenyltransferase Substrates and Defining Substr......Page 232
C. albicans Prenyltransferases......Page 239
Conclusions......Page 241
Protein Geranylgeranyltransferase-I Structure and Reaction Cycle......Page 255
Determinants of Ca1a2X Substrate Selection in FTase and GGTase-I......Page 258
Structure of Candida albicans Protein Geranylgeranyltransferase-I......Page 259
FTase Inhibitors for Treatment of Malaria and Other Infectious Diseases......Page 266
References......Page 268
Abstract......Page 273
Introduction......Page 274
FTase......Page 276
GGTase-I......Page 279
Concluding Remarks......Page 284
References......Page 286
Targeting Ras with Farnesyl Transferase Inhibitors......Page 290
Discovery of Farnesyl Transferase Inhibitors......Page 291
Alternative Prenylation of K-Ras and N-Ras......Page 295
Rheb......Page 299
CENP-E and -F......Page 300
Clinical Studies of FTIs in Cancer......Page 301
Pharmacodynamic Activity......Page 303
Identification of FTI-Responsive Patients......Page 304
Hutchinson-Gilford Progeria Syndrome: A Disease of Farnesylation?......Page 305
Conclusions and Other Therapeutic Opportunities for FTIs......Page 307
References......Page 308
Author Index
......Page 319
Index
......Page 351