Inhibitors of Cell Growth

References.- The Growth-Inhibitory Effects of TGF?.- 1 Introduction.- 2 The Eukaryotic Cell Cycle.- 3 Effects of TGF? on Cell-Cycle Progression.- 3.1 TGF? Inhibition of CDK and Cyclin Expression.- 3.2 TGF? Effects on p15 Activity.- 3.3 TGF? Effects on p27 Activity and CDKI Distribution.- 4 Conclusions.- References.- Big Brothers Are Watching: the Retinoblastoma Family and Growth Control.- 1 Introduction.- 2 Interaction of Retinoblastoma Family Proteins with the Transcription Factor E2F.- 3 Structure and Expression of Retinoblastoma Family Members.- 4 Growth Inhibition by Retinoblastoma Family Members.- 5 Effects of Deletions of RB Family Members on Mice Development.- 6 Regulation of RB Family Members by Cyclin/CDK complexes — the Restriction Point.- 7 Role of pRB in Growth-Promoting Pathways.- 8 Role of pRB in Growth-Inhibiting Pathways; Apoptosis and Differentiation.- 8.1 pRB as a Downstream Effector of p53.- 8.2 RB Family Members in Differentiation.- 8.3 RB Family Members in TGF ?-Mediated Growth Inhibition.- 9 RB2/130 and p107 Confer a Growth Suppressive Ability, Other than pRB.- 10 pRB Inhibits Biosynthesis Via Inhibiting RNA pol I and pol III-Dependent Transcription.- 11 RB Family Members Interact with Several Other Growth-Regulating Genes.- 12 Concluding Remarks.- References.- The Growth-Regulatory Role of p21(WAF1/CIP1).- 1 Introduction.- 2 p21-Induced Growth Arrest Is Mediated Through Protein-Protein Interactions.- 2.1 p21 Promotes Cell-Cycle Arrest via Interactions with Cdks and PCNA.- 2.2 Proteins Other than Cdks and PCNA that Bind p21.- 2.3 Protein Interaction Domains of p21.- 3 p21 Expression During Development and Differentiation.- 4 Growth Suppression by p21.- 5 p21 Expression and Apoptosis.- 6 Regulation of p21 Expression.- 6.1 p53-Dependent Regulation of p21 Transcription.- 6.2 p53-Independent Activation of p21 Promoter.- 6.3 Repression of p21 Promoter Activity.- 7 p21 and Transcriptional Activation of Downstream Genes.- 8 p21 and Cancer.- References.- Mechanisms of Cell Cycle Blocks at the G2/M Transition and Their Role in Differentiation and Development.- 1 Introduction.- 2 Cdk Kinases and Cell-Cycle Control.- 3 Basic Controls of Cdc2 Kinase Activity.- 3.1 Positive Control of Cdc2 Kinase.- 3.2 Negative Control of Cdc2.- 3.2.1 Inhibitory Phosphorylations.- 3.2.2 Control of the Controllers.- 3.3 Negative Regulators of Cdc2.- 4 Mechanisms of Negative Control at G2/M.- 5 Oncogenes and Tumor-Suppressor Genes in G2 Arrest.- 6 G2/M Blocks in Meiosis.- 6.1 Oocyte Maturation.- 6.2 Release from Meiosis I.- 6.3 Control of Meiosis II.- 6.4 Mouse Oogenesis and Spermatogenesis.- 7 G2 Blocks During Development.- 7.1 String, Twine, and Drosophila Development.- 8 G2 Blocks in Differentiation.- 8.1 Polyploidy and Endoreduplication.- References.- Mechanisms of Interferon Action.- 1 Introduction.- 2 The Interferon Proteins and Genes.- 2.1 Classification and Biological Properties.- 2.2 Evolution of the IFN Genes.- 2.3 Tissue Distribution and Regulation of IFN Gene Expression.- 2.3.1 Type I IFN Genes.- 2.3.2 The IFN? Gene.- 3 The Interferon Receptors.- 3.1 The Cytokine Receptor Superfamily.- 3.2 The Type I IFN Receptor Complex.- 3.3 The Type II IFN Receptor Complex.- 4 IFN-Dependent Signaling Pathways.- 4.1 Identification of IFN-Dependent Signaling Factors.- 4.1.1 The JAKs.- 4.1.2 The STATs.- 4.2 Type II IFN Signaling.- 4.3 Type I IFN Signaling.- 4.4 Other IFN-Induced Signaling Components.- 5 IFN-stimulated Genes.- 5.1 Kinetics of ISG Induction.- 5.2 Mediators of Antiviral Responses.- 5.2.1 The 2,5-Oligoadenylate Synthetases.- 5.2.2 The Mx Proteins.- 5.2.3 The dsRNA-Induced Kinase PKR.- 5.2.4 IFN-Regulatory Factors.- 5.3 IFN Regulation of Cell-Cycle Components.- 6 Therapeutic Potentials of the IFNs.- 6.1 Cancers.- 6.2 Viral Diseases.- 6.3 Other Diseases.- 7 Interferons as Hormones of Pregnancy.- 8 Conclusion.- References.- Growth-Inhibiting N-Substituted Endogenous Peptides.- 1 Introduction.- 2 Purification and Characterization of Endogenous Growth Inhibitors.- 2.1 Early Attempts at Purification.- 2.2 Structure and Biological Properties of Endogenous Bone Marrow Growth-Inhibiting Peptides.- 2.3 Structure and Biological Properties of the Inhibitory Epidermal Pentapeptide.- 3 Other N-Substituted Inhibitory Oligopeptides.- 3.1 Inhibitory Oligopeptides in Liver, Colon, and Melanocytes.- 3.2 Inhibitory N-Substituted Oligopeptides Not Related to Specific Organs/Tissues.- 4 N-Substituted Inhibitory Oligopeptides in Neoplasia.- 4.1 Carcinogenesis.- 4.2 N-Substituted Inhibitory Oligopeptides and Tumors.- 5 Purification Procedures Used for Characterization of N-Substituted Peptides.- 5.1 Extraction and Chromatography Systems.- 5.2 Biochemical Characterization of Peptides.- 5.3 Criteria for Purity.- 5.4 Criteria for Identity Between Native and Synthetic Peptides.- 6 „Chalones“ and Inhibitory N-Substituted Oligopeptides: Similarities and Differences.- 7 Possible Strategies for Clinical Use of Endogenous Growth Inhibitors.- 7.1 Possible Use of Endogenous Inhibitors in Medicine.- 7.2 Possible Use of Stimulating Dimers and Peptidomimetics.- 8 Concluding Remarks.- References.- Endogenous Angiogenesis Inhibitors: Angiostatin, Endostatin, and Other Proteolytic Fragments.- 1 Introduction.- 2 Angiostatin.- 2.1 Discovery.- 2.2 Structure and Generation.- 2.3 Antiendothelial, Antiangiogenic and Antitumor Effects.- 2.4 Kringle 5.- 3 Endostatin.- 3.1 Structure.- 3.2 Antiangiogenic and Antitumor Activities.- 4 Other Angiogenesis Inhibitors.- 4.1 Endogenous Inhibitors.- 4.2 Proteolytic Fragments.- 4.3 Small Peptides.- 5 Clinical Applications.- References.- Inhibitors of Preadipocyte Replication: Opportunities for the Treatment of Obesity.- 1 Introduction.- 2 Preadipocytes.- 3 Relationship Between Host Characteristics and Adipose Cell Dynamics.- 4 Control of Preadipocyte Replication.- 5 Potential Therapeutic Strategies.- References.- Growth Inhibitors for Mammary Epithelial Cells.- 1 Introduction.- 2 The Role of Transforming Growth Factor-? (TGF-?) in Mammary Gland Development.- 2.1 TGF-? Is a Multifunctional Factor of Normal Mammary Gland Development.- 2.1.1 TGF-?-Can Act Exogenously on Mammary Development in Vivo.- 2.1.2 Evidence for Endogenous TGF-? in the Mammary Gland.- 2.1.3 In Vitro Studies for TGF-? Activity.- 2.2 TGF-? Is a Growth Inhibitor Modulating Differentiation of the Mammary Gland.- 2.2.1 TGF-?s Role in Mammary Gland Tumorigenesis.- 2.2.2 Alterations in TGF-? Production.- 2.2.3 Data Against TGF-?s as Biologically Important Autocrine Growth Inhibitors of Human Breast Carcinoma Cells.- 2.2.4 Alterations in Growth Response of Mammary Edpithelial Cells by TGF-?.- 2.3 TGF-? Is a Paracrine Growth Factor (Effects on Stromal Cells).- 2.3.1 Extracellular Matrix.- 2.3.2 Stromal Epithelial Interactions.- 2.3.3 Implications of Tumor Development, Invasion, and Metastasis.- 2.4 Relationship of TGF-? and Steroid Hormones.- 2.4.1 Steroid Hormones Regulate TGF-? Production by Breast Cancer Cells.- 3 Mammary-Derived Growth Inhibitor (MDGI).- 3.1 Purification.- 3.1.1 Structural Features and Relationship to Fatty Acid-Binding Proteins.- 3.2 Biological Activities.- 3.2.1 Growth Inhibition of Mammary Epithelial Cells.- 3.2.2 Stimulation of Differentiation.- 3.2.3 Desensitization of Beta-Adrenergic Receptors.- 3.3 Expression of MDGI.- 3.3.1 Developmental Regulation in the Bovine Mammary Gland.- 3.3.2 Hormonal Dependence of Expression in Mouse Organ Culture.- 3.4 Nuclear Localization.- 4 Tumor Necrosis Factor Alpha (TNF-?).- 4.1 TNF-? Structure and Function in Breast Tissue.- 4.2 Hormone Dependence of TNF-Related Effects in Mammary-Derived Cells.- 4.3 Expression of TNF-? in Breast Cancer.- 5 Conclusion.- References.- Growth Inhibition of Human Fibroblasts in Vitro.- 1 Introduction.- 2 Mechanisms Responsible for Contact Inhibition of Growth.- 2.1 Conformational Flexibility.- 2.1.1 Inhibitory Glycopeptides.- 2.1.2 Further Evidence for the Presence of Growth Inhibitors.- 3 Mechanisms Responsible for the Terminal Postmitotic Stage of Human Fibroblasts.- 3.1 Structural Modifications.- 3.1.1 Energy Transduction Mechanisms.- 3.1.2 Putative Growth Inhibitors and Failure to Induce Positive Growth Factors.- References.