NEW DEVELOPMENTS IN PROTEOMICS RESEARCH

NEW DEVELOPMENTS IN PROTEOMICS RESEARCH

CONTENTS

PREFACE

Chapter 1 THE SERINE PROTEINASE INHIBITOR Z ALPHA-1 ANTITRYPSIN: ACTING ON THE NF-KAPPAB SYSTEM FOR CYTOTOXICITY

ABSTRACT

INTRODUCTION

A1AT: THE MOLECULE

THE Z DISEASE PRONE VARIANT OF A1AT

CLINICAL MANIFESTATION OF Z A1AT DEFICIENCY

Lung Disease

Liver Disease

NFB

MECHANISTIC REGULATION OF NFB ACTIVATION

Z A1AT Intracellular Pathways of Cytotoxicity

HISTONE CODE: A NEW APPROACH FOR THE UNDERSTANDING OF Z A1AT INDUCED NFB

REFERENCES

Chapter 2 THE STRUCTURE OF 1-PROTEINASE INHIBITOR POLYMER: FACTS AND HYPOTHESES

ABSTRACT

INTRODUCTION

ESTABLISHED HYPOTHESES

FACTS

AN ALTERNATIVE MODEL

ACKNOWLEDGMENTS

REFERENCES

Chapter 3 THE ROLES OF MAMMALIAN MITOGEN-ACTIVATED PROTEIN KINASE-ACTIVATING PROTEIN KINASES (MAPKAPKS) IN CELL CYCLE CONTROL

ABSTRACT

1. THE CELL CYCLE

2. THE MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) PATHWAY

3. THE ROLE OF MAPKAPK IN CELL CYCLE REGULATION

3.1. P90 Ribosomal S6 Kinase or RSK

3.1.1. Properties and Function of RSK

3.1.2. The role of RSK in Cell Cycle Regulation

General Observations that Suggest a Role for RSK in Cell Cycle Regulation

The Role of the Cytostatic Factor (CSF) and the Anaphase-Promoting Complex/Cyclosome (APC/C) in Oocyte Maturation

The Effect of RSK on the Spindle Check Point Component Bub1

RSK and the APC/C Inhibitor Early Mitotic Inhibitor 2 (Emi2)

RSK and Cyclin B

RSK and the Cdk Activator Cdc25

The Role of RSK in Oocyte Maturation of other Species

Other Mechanisms by which RSK May Interfere with Cell Cycle Progression

3.2. MSK1 and MSK2

3.2.1. Properties and Functions of MSK1 and MSK2

3.2.2. The Role of MSK1 and MSK2 in Cell Cycle Regulation

3.3. MNK1 and MNK2

3.3.1. Properties and Function of MNK1 and MNK2

3.3.2. The Role of MNK1 and MNK2 in Cell Cycle Regulation

3.4. MK2

3.4.1. Properties and Function of MK2

3.4.2. The Role of MK2 in Cell Cycle Regulation

3.5. MK3

3.5.1. Properties and Function of MK3

3.5.2. The Role of MK3 in Cell Cycle Regulation

3.6. MK5

3.6.1. Properties and Function of MK5

3.6.2. The Role of MK5 in Cell Cycle Regulation

4. MAPKAPK INHIBITORS AND THERAPEUTIC APPLICATIONS

CONCLUSION

ACKNOWLEDGMENTS

REFERENCES

Chapter 4 STUDY OF FOLDING/UNFOLDING KINETICS OF LATTICE PROTEINS BY APPLYING A SIMPLE STATISTICAL MECHANICAL MODEL FOR PROTEIN FOLDING

ABSTRACT

1. INTRODUCTION

2. METHOD

2.1. Three-Dimensional Lattice Proteins

2.2. Statistical Mechanical Model for Protein Folding and Unfolding

2.3. Calculation of Folding and Unfolding Rates

2.4. Single Amino Acid Substitutions

2.5. Φ Value Analysis

3. RESULTS

3.1. Folding and Unfolding Rates

3.2. The  Value and Folding Nucleus

3.3. Changes in the Folding and Unfolding Rates

4. DISCUSSION

4.1. Folding Nucleus and Short-Range Interactions

4.2. Contact Order and Long-Range Interactions

4.3. Unfolding Rate and Long-Range Interactions

4.4. Fractional  Values

4.5. Negative  Values

CONCLUSION

REFERENCES

Chapter 5 INTRINSICALLY UNORDERED PROTEINS: STRUCTURAL PROPERTIES, PREDICTION AND RELEVANCE

ABSTRACT

1. INTRODUCTION

2. PREDICTION METHODS OF PROTEINS UNORDERED REGIONS

2.1. Per-Residue Prediction Methods

2.1.1. PONDR

2.1.2. DisEMBL

2.1.3. GlobPlot

2.1.4. Drippred

2.1.5. Disopred2

2.1.6. FoldUnfold

2.1.7. DISpro

2.1.8. FoldIndex

2.1.9. PreLink

2.1.10. RONN

2.1.11. IUPred

2.1.12. SPRITZ

2.1.13. TOP-IDP

2.1.14. DISOclust

2.2. Binary Classification Methods

2.2.1. CH-plot

2.2.2 Nn-Cdf

2.2.3. Predispro

2.3. Prediction of Protein Binding Regions in Unordered Proteins

3. ASSESSMENT OF DISORDER PREDICTION IN CASP COMPETITION

4. RELEVANT PROTEINS RECENTLY FOUND TO BE INTRINSICALLY UNORDERED

4.1. Human Sirt-1

4.2. Chemokine Membrane Receptors

4.2.1. Sequence Analysis

4.2.2. Unordered Region Prediction

CONCLUSION

REFERENCES

Chapter 6 PROTEIN DISULPHIDE ISOMERASES: DIVERSITY AND ROLES IN PLANTS

ABSTRACT

ABBREVIATIONS

INTRODUCTION

1. BIOCHEMICAL CHARACTERISTICS OF PDILS

1.1. Composition of the TRX Superfamily and PDIL Family

1.2. Biochemical Structures of Protein Disulphide Isomerases

1.3. Primary Biochemical Activity of PDI

2. THE HUMAN PDIL FAMILY

2.1. Composition and Structural Diversity of Human PDILs

2.2. Functions of PDILs in Human and other Mammals

3. PDI IN CHLAMYDOMONAS REINHARDTII

4. DIVERSITY OF PLANT PDILS

4.1. PDILs in Arabidopsis Thaliana

4.2. PDILs in Soybean

4.3. PDILs in other Dicots

4.4. PDILs in Cereals

5. FUNCTIONS OF PDILS IN PLANTS

5.1. Roles of PDI in Assortment and Deposition of Seed Storage Proteins in Plants

5.1.1. Roles in Seed Storage Protein Processes and ER Stress in Dicots

5.1.2. Roles in Seed Storage Protein Processes and ER Stress in Cereals

5.2. Roles of PDILs in Plant Development

5.2.1. Roles in Chloroplast Biogenesis/Photosynthetic Apparatus or Processes

5.2.2. Roles in Reproductive Tissues and Seed Development

5.3. Roles of PDILs In Response to Other Abiotic and Biotic Stresses in Plants

5.4. Other Roles of PDILs in Plants

CONCLUSION

REFERENCES

Chapter 7 FOLDING AND UNFOLDING OF HYPERTHERMOPHILIC PROTEINS: MOLECULAR BASIS OF ADAPTATION TO HOT ENVIRONMENT

ABSTRACT

INTRODUCTION

1. EQUILIBRIUM UNFOLDING AND FOLDING OF HYPERTHERMOPHILIC PROTEINS

Ribonuclease HII

Cold Shock Protein from Thermotoga Maritima

2. CONTRIBUTION OF THE STABILIZATION FACTORS TO THE SLOW UNFOLDING OF HYPERTHERMOPHILIC PROTEIN

Internal Hydrophobic Interactions

Effect of Proline at N-Terminal -Helices

Effect of Naturally Occurring Osmolytes

3. ACTIVITY-STABILITY TRADE-OFF OF HYPERTHERMOPHILIC PROTEIN

4. PROPEPTIDE- AND CA2+-MEDIATED FOLDING OF HYPERTHERMOSTABLE SUBTILISIN

Activity and Thermal Stability of Tk-Subtilisin

Role of Ca2+

Role of Propeptide

5. PROTEIN FOLDING IN TERMS OF ADAPTATION TO HIGH TEMPERATURE

CONCLUSION

ACKNOWLEDGMENTS

REFERENCES

Chapter 8 RIBOSOME ASSISTED PROTEIN FOLDING: SOME OF ITS BIOLOGICAL IMPLICATIONS

1. THE PROTEIN FOLDING PROBLEM

1.1. Protein Folding Inside the Cell

1.2. Ribosome Based Protein Folding System

1.3. The Ribosome and Its Peptidyl Transferase Center

1.4. Conformation of Nascent Protein Inside the Exit Tunnel

2. RIBOSOME IN PROTEIN FOLDING

2.1. Ribosome: A General Protein Folding Modulator

2.2. Refolding of Unfolded Proteins by Ribosomal Components: In Vitro Studies

2.3. Ribosome Assisted Protein Folding: In Vivo Studies

2.4. Unfolded Protein Splits 70S to Interact with 50S Subunit for Its Folding: In Vitro and in Vivo Stidies

3. THE SEARCH FOR A MECHANISM OF DOMAIN V RRNA ASSISTED FOLDING

3.1. Identification of Sites on Domain V RNA Where Proteins Bind during Refolding

3.2. Identification of Specific Amino Acids in BCA and Lysozyme that Interact with Nucleotides in Domain V RNA

3.3. Specific Interaction Between the Amino Acids of Unfolded Protein and the Nucleotides of Domain V rRNA: An Explanation of Ribosome Assisted Protein Folding

4. SEQUENTIAL STEPS OF RIBOSOME MEDIATED PROTEIN FOLDING: SUMMARY OF THE WHOLE PROCESS

REFERENCES

Chapter 9 PROTEIN KINASE INHIBITORS IN CANCER

ABSTRACT

PROTEIN KINASE

PROTEIN KINASES AND CANCER

PRINCIPLES OF DESIGNING PROTEIN KINASE INHIBITORS

PROTEIN KINASE INHIBITORS IN CANCER TREATMENT

REFERENCES

Chapter 10 PROTEIN KINASE INHIBITORS IN THE TREATMENT OF MALIGNANT LIVER AND KIDNEY TUMORS

ABSTRACT

INTRODUCTION

Pathogenesis of Hepatocellular Carcinoma and Current Treatment Options Offered by Tyrosine Kinase Inhibitors

Pathogenesis of Renal Cell Carcinoma and Current Treatment Options Offered by Tyrosine Kinase Inhibitors

REFERENCES

INDEX