Main description:

Studies have identified important families of proteins (denoted: heat shock or stress proteins, Hsps) which display an enhanced expression in response to heat shock or other physiological stresses. Besides the characterization of the genes encoding Hsp and the mechanisms of their induction, recent studies have concentrated on the function of these proteins. It was shown that the expression of Hsp protects the cell against different types of aggressions. In addition,Hsp can regulate essential biochemical processes in unstressed cells. For example, members of the Hsp60 and Hsp70 families act as ATP-binding proteins allowing the folding of nascent or denatured proteins as well as the assembly or disassembly of protein complexes. These observations have led to the discovery of the molecular chaperone concept (Ellis and Hemmingsen 1989). Amongst the proteins whose expression is up-regulated by heat shock or other types of stresses are the small stress proteins also denoted (sHsps, sHsp or sHSP). Small stress proteins encompass a large numbers of related proteins which are represented in virtually all organisms, including prokary- otes.
These polypeptides share a structural domain, often referred to as the a-crystallin domain, common to the lens protein alpha-crystallin (Ingolia and Craig 1982;Wistow 1985). In addition to being increased in response to several types of stresses, the Hsp level is also upregulated during development and correlates with the differentiation and oncogenic status of the cell. In spite of the fact that sHsp can confer cellular protection against stresses,their molecular function has remained enigmatic for years.

Contents:

Evolution and Diversity of Prokaryotic Small Heat Shock Proteins.- 1 Introduction.- 2 sHsps in Prokaryotes.- 3 Are sHsps Dispensable in Some Pathogenic Bacteria?.- 4 Phylogenetic Analysis of Prokaryotic sHsps.- 5 Lateral Transfer or Convergent Evolution of Prokaryotic sHsp Genes.- 6 Secondary Structure Prediction of the a-Crystallin Domain.- 7 Alignment and Secondary Structure Prediction of the N-Terminal Domain.- 8 Summary and Concluding Remarks.- References.- Discovery of Two Distinct Small Heat Shock Protein (HSP) Families in the Desert Fish Poeciliopsis.- 1 Introduction.- 2 Variation in Small HSPs Among Desert Species of Poeciliopsis.- 2.1 Results of Survey Among Species.- 2.2 HSP Isoforms as Primary Gene Products.- 2.3 Conclusions.- 3 Variation in Small HSPs Within Poeciliopsis Species.- 3.1 Results of Within-Species Survey.- 3.2 Conclusions.- 4 Discovery of Two Classes of Small HSPs in a Single Taxon.- 4.1 Differential Synthesis.- 4.2 Phosphorylation State of the Small HSPs.- 4.3 Sequence Analysis.- 4.4 Evolutionary Analysis.- 4.5 Conclusions.- References.- Chaperone Function of sHsps.- 1 Introduction.- 2 General Aspect of Chaperone function.- 2.1 Chaperones.- 2.2 Analysis of Chaperone function.- 3 The Chaperone Properties of sHsps.- 3.1 In Vivo Functions of sHsps.- 3.2 sHsps Bind Non-Native Protein.- 3.3 Complex Formation and Substrate Range.- 3.4 The Substrate Binding Site.- 3.5 Mechanism of Substrate Binding.- 3.6 Regulation of Functional Properties.- 3.7 sHsps in the Context of the Cellular Chaperone Machinery.- 4 Conclusions.- References.- The Small Heat Shock Proteins of the Nematode Caenorhabditis elegans: Structure, Regulation and Biology.- 1 Introduction.- 2 The Small Heat Shock Protein Family of C. elegans.- 3 The 16-kDa Stress Proteins (Hspl6s).- 3.1 Hspl6 Gene Organization.- 3.2 Hspl6 Regulation.- 3.3 Biochemical Properties of Hspl6s.- 3.4 Uses of Hspl6 Promoters in C. elegans Research.- 4 The 12-kDa Small Heat Shock Proteins (Hspl2s).- 5 SIP-1.- 6 Hspl7.5.- 7 Hsp25.- 8 Hsp43.- 9 Conclusions and Prospects.- References.- Drosophila Small Heat Shock Proteins: Cell and Organelle-Specific Chaperones?.- 1 Introduction.- 2 Members of the Small Heat Shock Proteins Family.- 3 Transcriptional Regulation.- 3.1 Organisation of Chromatin.- 3.2 Stress-Induced Activation by the Heat Shock Factor.- 3.3 Developmental Transcription of shsp Genes.- 3.3.1 Regulation Cascade Induced by Ecdysone.- 3.3.2 Tissue- and Cell-Specific Enhancers.- 4 Intracellular Localisation-Analysis of Targeting Signals.- 5 Biochemical Properties and Post-Translational Modifications.- 6 Stress-Induced Expression of sHsp.- 6.1 Cell-Specific Response of sHsp.- 6.2 Functions of sHsp Under Stress Conditions.- 7 Developmental Expression of sHsp.- 7.1 Stage, Tissue, and Cell Specificity.- 7.1.1 Embryogenesis.- 7.1.2 Germ Line.- 7.1.3 Ageing.- 7.2 Functions of sHsp During Normal Development.- 7.2.1 Interaction with the SUMO-Conjugating Enzyme Ubc9.- 7.2.2 Modulation of Specific Biological Activity.- 8 Conclusion.- References.- The Developmental Expression of Small HSP.- 1 Introduction.- 2 Small HSP in Extraembryonic Development.- 3 Small HSP in Ectodermal Lineages.- 3.1 Neural Crest Cell Derivatives.- 3.2 Neurectoderm.- 3.3 Expression in the Skin.- 4 Small HSP in Mesodermal Lineages.- 4.1 Small HSP in Muscle Development.- 4.1.1 The Expression Pattern of sHSP in the Heart.- 4.1.2 The Expression Pattern of sHSP in Skeletal and Smooth Muscle.- 4.1.3 The Subcellular Localization of sHSP in Muscle.- 4.2 Small HSP in Other Mesodermal Lineages.- 4.2.1 Expression in Cartilage and Bones.- 4.2.2 Expression in the Derivatives of the Notochord.- 4.2.3 Expression in the Kidney.- 4.2.4 Expression in the Adrenal Glands.- 4.2.5 Expression in the Gonads.- 4.2.6 Expression in the Blood Cells.- 5 Small HSP in Endodermal Lineages.- 5.1 Expression in the Upper Digestive Tract.- 5.2 Expression in the Stomach And Intestine.- 5.3 Expression in the Bladder.- 6 Phosphorylation of sHSP During Development.- 7 Developmental Regulation of Small HSP Gene Expression.- 7.1 Regulation of ?A-crystallin Gene Transcription.- 7.2 Regulation of ?B-crystallin Gene Transcription.- 7.3 Regulation of HSP25 Gene Transcription.- 8 The Role of Small HSP in Development and Differentiation.- 8.1 The Chaperone function.- 8.2 The Direct or Indirect Actin-Binding Property.- 8.3 Small HSP and Intermediate Filaments.- 8.4 Small HSP and Apoptosis.- 8.5 Small HSP and the Response to Stress.- 8.6 Small HSP and Protein Degradation.- 9 Small HSP in the Development of Non-Mammals.- References.- Expression and Phosphorylation of Mammalian Small Heat Shock Proteins.- 1 Introduction.- 2 Modification of the Expression of Hsp27 and ?B-crystallin.- 2.1 Stimulation of Stress-Induced Expression of Hsp27 and ?B-crystallin by Modulators of the Arachidonic Acid Cascade.- 2.2 Modulation of Expression of Hsp27 and ?B-crystallin by Protein Kinases.- 2.3 Modulation of Expression of Hsp27 and ?B-crystallin by the Cellular Redox State.- 3 Phosphorylation of Small Hsps.- 3.1 Phosphorylation of Hsp27.- 3.1.1 Phosphorylation and Dissociation of Hsp27.- 3.2 Phosphorylation of Hsp20.- 3.3 Phosphorylation of ?B-crystallin.- 3.3.1 Phosphorylation of ?B-crystallin in Response to Stress and Enzymatic Activities Responsible for Phosphorylation.- 3.3.2 Phosphorylation of ?B-crystallin in Mitotic Cells.- References.- sHsp-Phosphorylation: Enzymes, Signaling Pathways and Functional Implications.- 1 Introduction.- 2 Identification of Phosphorylated sHsps.- 3 The Major Pathway for sHsp Phosphorylation Via p38 MAPK and MAPKAP Kinase 2.- 4 Other Pathways.- 5 Functional Aspects of sHsps-Phosphorylation.- 5.1 Phosphorylation and Oligomerisation.- 5.2 Speculations About the Function of sHsp Phosphorylation.- References.- Small Stress Proteins: Modulation of Intracellular Redox State and Protection Against Oxidative Stress.- 1 Introduction.- 2 Cell Death Induced in Response to Oxidative Stress.- 3 sHsp Expression Protects Against Oxidative Stress-Induced Cell Death.- 3.1 Expression of sHsp Can Modulate the Intracellular Redox State.- 3.2 In Murine Fibroblasts Hsp27 Modulates Glutathione Level and Intracellular Redox State Through Upregulation of Glucose 6-Phosphate Dehydrogenase Activity.- 3.3 Hsp27 Expression Protects Against Protein Oxidation and the Inactivation of Key Anti-Oxidant Enzymes.- 3.4 Oligomerization as a Key Property Regulating sHsp Protective Activity Against Oxidative Stress.- 4 sHsp Expression Can Also Enhance Oxidative Stress Induced Cell Death.- 5 Conclusions and Future Perspectives.- References.- Small Stress Proteins: Novel Negative Modulators of Apoptosis Induced Independently of Reactive Oxygen Species.- 1 Introduction.- 2 sHsp Expression Protects Against Apoptosis Induced Independently of ROS Formation.- 2.1 Hsp27 Interferes with the Apoptotic Machinery Downstream of Cytochrome c Release from Mitochondria.- 2.2 Hsp27 Interferes with the Release of Cytochrome c from the Mitochondria: A Possible Consequence of the Modulation of a Cytoskeleton to the Mitochondria Apoptotic Pathway.- 2.3 Hsp27 Interferes with Apoptosis Induced by Death Ligands.- 2.4 Hsp27 Expression Generates Protection Against Heat Shock-Induced Apoptosis.- 2.5 Role of Hsp27 Phosphorylation and Oligomerization in the Protection Against Apoptosis.- 3 Hsp27 as Essential Anti-Apoptotic Protein During Early Cell Differentiation.- 4 Hsp27 Modulates Apoptosis in Vivo and Enhances the Tumorigenicity of Transformed Cells.- 5 Conclusions and Future Perspectives.- References.- Hsp27 as a Prognostic and Predictive Factor in Cancer.- 1 Introduction.- 2 Female Genital Tract.- 2.1 Breast.- 2.2 Endometrium, Ovary/Uterine Cervix.- 3 Nervous System and Digestive Tract.- 4 Hematological Malignancies.- 5 Genitourinary Tract.- 6 Tumors from Others Tissues.- 7 Conclusion.- References.- Cytoskeletal Competence Requires Protein Chaperones.- 1 Symmary.- 2 Human Diseases Caused by sHSF Mutations.- 2.1 Protein Inclusions Involving the Cytoskeleton and sHSPs.- 2.2 Cardiomyopathies and Eye Lens Cataract.- 3 sHSP Interaction with the Cytoskeleton.- 3.1 Association with Actin and Regulation of the Interaction.- 3.2 Interaction with Cytoskeleton Associated Proteins.- 3.3 Intermediate Filament and Microtubule Association.- 4 Functional Implications of the Interactions.- 4.1 Cell stress Identifies an Important Link Between Chaperones and the Cytoskeleton.- 4.2 sHSP Regulation of the Cytoskeleton in Unstressed Cells.- 5 The Chaperone-Cytoskeleton Complex. The Guardian of the Cytoplasm?.- References.- Hsp27 in the Nervous System: Expression in Pathophysiology and in the Aging Brain.- 1 Introduction.- 2 Constitutive Expression of Hsp27 in the Nervous System.- 2.1 Central Nervous System: Hsp27 in the Brain and Spinal Cord.- 2.2 Peripheral Nervous System.- 2.2.1 Dorsal Root Ganglia and Nodose Ganglion.- 2.2.2 Cardiac Neurons.- 3 Expression of Hsp27 in Pathophysiology.- 3.1 Heat Shock and Fever.- 3.2 Kainic Acid-Induced Seizures.- 3.3 Cortical Spreading Depression.- 3.4 Ischemia/Preconditioning and Cell Survival.- 3.5 Peripheral Nerve Injury.- 4 Expression of Hsp27 in Diseases of the Aging Brain.- 4.1 Neurodegenerative Diseases.- 4.2 Brain Tumors.- 5 Conclusions.- References.- Protection of Neuronal and Cardiac Cells by HSP27.- 1 Protective Effect of Heat Shock Proteins.- 2 Protective Effect of HSP27.- 3 Protective Effect of HSP27 in Neuronal and Cardiac Cells.- 3.1 Neuronal Cells.- 3.2 Cardiac Cells.- 4 Conclusion.- References.