Hedgehog Signaling

Former Editors

Contributors

Preface

Chapter One: Hedgehog Signaling

I. Hedgehog Ligands

II. Hedgehog Signaling

III. Hedgehog Signaling in Zebrafish Eye Vesicle Patterning

IV. Hedgehog Signaling in Zebrafish Photoreceptor Differentiation

V. Hedgehog Signaling in Zebrafish Inner Nuclear Layer

VI. Hedgehog Signaling in Zebrafish Ganglion Cell Differentiation

Chapter two: Canonical and Noncanonical Hedgehog/GLI Signaling in Hematological Malignancies

I. Hedgehog Introduction

II. Regulation of Canonical HH Signaling and Its Implication in Cancer

III. SMO-Independent Modulation of GLI Activity

IV. Hedgehog in Hematopoiesis and Hematopoietic Stem Cells

V. From HSC to CML

VI. T- and B-Cell Malignancies

VII. Outlook

Chapter three: Noncanonical Hedgehog Signaling

I. Definition

II. Type I Noncanonical Signaling: Pathways Engaged Exclusively by Ptc1

III. Type II Noncanonical Signaling: Pathways Engaged by Smoothened

IV. Noncanonical Hh Signaling in Drosophila

V. Concluding Remarks

Chapter four: Gli Protein Nuclear Localization Signal

I. Introduction

II. Nuclear Localization Signal and Nuclear Export Signal

III. NLS and NES Mapping

IV. Sequence Comparison of Gli NLSs—NLSs in ZF Domains

V. Predicted 3D Structure of Gli NLS

VI. NLS Control of Gli/Ci Subcellular Localization in Hh Signaling

VII. Perspectives

Chapter five: Mammalian Homologues of Drosophila Fused Kinase

I. Introduction

II. The Major Steps of Hh Signaling

III. Ci/Gli Proteins are Transcription Factors Mediating Hh Activities

IV. Hedgehog Signaling Complex is Responsible for Regulation of ci Protein

V. Regulation of Gli Proteins

VI. Fu is a Protein Kinase Playing Catalytic and Regulatory Roles in ci regulation

VII. Protein Kinases Participating in the Regulation of Gli Proteins

VIII. Controversial Roles of Stk36

IX. The Role of Ulk3 in Shh Signaling Pathway

X. An Emerging Shh Signaling Model Involving Ulk3

Chapter six: Identification, Functional Characterization, and Pathobiological Significance of GLI1 Isoforms in Human Cancers

I. Introduction

II. Structures and Properties of GLI1 Isoforms

III. Regulation of GLI1 Isoforms by Canonical and Noncanonical Pathways

IV. GLI1 Isoforms and Malignant Phenotypes of Cancer

V. Conclusion and Future Directions

Chapter seven: Gli-Similar Proteins

I. Introduction

II. Mechanism of Action of Glis Proteins

III. Role of Glis Proteins in Renal Physiology and Pathology

IV. Role of Glis3 in Pancreas Physiology and Pathology

V. Glis Functions in Other Tissues

VI. Conclusion

Chapter eight: Sonic Hedgehog Regulates Wnt Activity During Neural Circuit Formation

I. Introduction

II. Shh and Wnt Signaling: Canonical Signaling Pathways

III. Patterning and Morphogenesis of the Neural Tube

IV. Establishment of Neuronal Polarization

V. Axon Guidance

VI. Synapse Formation

VII. Other Factors Influencing Shh and Wnt Pathways

VIII. Conclusions and Future Directions

Chapter nine: Hedgehog/Gli Control by Ubiquitination/Acetylation Interplay

I. Introduction

II. Ubiquitin-Dependent Regulation of Hh Signaling

III. Increasing the Complexity of Hh Signaling in Vertebrates: The Cul1- and Cul3-Dependent Ubiquitination Processes

IV. An Alternative Gli1 Control by the HECT-Type Itch E3 Ubiquitin Ligase-Based Processing

V. Activation of Itch Function by Numb

VI. Acetylation to Ubiquitination Connection in Hh Signaling

VII. Implications of Ubiquitin-Dependent Events for Cell Development and Tumorigenesis

VIII. Implications for Ubiquitination/Acetylation Interplay in Cell Development and Cancer Control

IX. Conclusions

Chapter ten: Palmitoylation of Hedgehog Proteins

I. Introduction to Protein Palmitoylation

II. Palmitoylation of Hedgehog Proteins

III. Palmitoylation of Other Secreted Proteins

IV. The MBOAT Family of Acyltransferases

V. Conclusions and Future Directions

Chapter eleven: Phosphorylation Regulation of Hedgehog Signaling

I. Introduction

II. Phosphorylation of the Transcription Factor in Hh Signaling

III. Phosphorylation of Smo Receptor in Hh Signaling

IV. Other Phosphorylation Events in Hh Signaling

V. Nonconserved Phosphorylation

VI. Phosphatases in Hh Signaling

VII. Differential Phosphorylation of Hh Signaling Components

Chapter twelve: Protein Kinase A Activity and Hedgehog Signaling Pathway

I. Introduction

II. Function of PKA in Hedgehog-Responsive Cells

III. Activation of PKA

IV. PKA Activity in Hedgehog-Responding Cells

V. Perspectives

Chapter thirteen: Phosphorylation of Gli by cAMP-Dependent Protein Kinase

I. Introduction

II. cAMP-Dependent Protein Kinase

III. Hedgehog Signaling and cAMP-Dependent Protein Kinase

IV. Gli Transcription Factors and cAMP-Dependent Protein Kinase

V. Conclusions

Chapter fourteen: ZFP932 Suppresses Cellular Hedgehog Response and Patched1 Transcription

I. Introduction

II. Zfp932 Characterization

III. ZFP932 Represses Ptch1 Expression

IV. ZFP932 Represses Cellular Hedgehog-Signaling Response

V. ZFP932 Regulates Osteoblast Differentiation

VI. Conclusion

Chapter fifteen: A New Era for an Ancient Drug

I. Historic Use of Arsenic in Medicine

II. Molecular Mechanisms of Arsenic in Cancer Therapy

III. Role of Hedgehog Signaling in Cancer

IV. Effect of Arsenic on Hh Signaling

V. Conclusions

Chapter sixteen: Aberrations and Therapeutics Involving the Developmental Pathway Hedgehog in Pancreatic cancer

I. Introduction

II. The Hedgehog Pathway

III. Hedgehog Therapeutics

IV. Conclusion

Chapter seventeen: Sonic Hedgehog Signaling and Potential Therapeutic Indications

I. Sonic Hedgehog Discovered (Shh)

II. Shh Signaling in Vertebrates

III. Shh Second Messenger Systems

IV. Shh in Stem Cell Proliferation

V. Shh in Oncogenesis

VI. Shh in Injury of the CNS

VII. Conclusion

Chapter eighteen: Sonic Hedgehog on Microparticles and Neovascularization

I. Introduction

II. Neovascularization

III. Sonic Hedgehog

IV. Microparticles

V. Conclusion

Chapter nineteen: “Patch”-ing up the Neurons

I. Introduction

II. The “Patched” Transmission

III. Ptch1 Expression in Neural Tissues

IV. Ptch1 in Disease, Development, and Injury

V. Conclusion

Chapter twenty: Activation of Hedgehog Pathway in Gastrointestinal Cancers

I. Introduction

II. Activation of the Hh Pathway in Esophageal Cancer

III. Activation of the Hh Pathway in Gastric Cancer

IV. Activation of the Hh Pathway in Colorectal Cancer

V. Summary

Chapter twenty-one: The Role of Sonic Hedgehog as a Regulator of Gastric Function and Differentiation

I. Introduction

II. Hh in the Adult Stomach

III. The Potential Role of Sonic Hh as a Gastric Hormone

IV. Conclusions and Future Directions

Chapter twenty-two: Sonic Hedgehog-Mediated Synergistic Effects Guiding Angiogenesis and Osteogenesis

I. General Introduction

II. General Aspects of Shh Signaling

III. The Role of Hh Morphogens in Bone Development and Repair

IV. Shh: Potential Candidate Linking Angiogenesis and Osteogenesis

V. Effects of Shh on Angiogenesis, Vessel Maturation, and Osteogenesis

VI. Coculture Models as In Vitro Models to Investigate Effects of Shh on Osteogenesis and Angiogenesis

VII. Effects of Shh on Angiogenesis in a Coculture Model

VIII. Effects of Shh on Osteogenesis in a Coculture Model

IX. Future Therapeutical Options and Delivery Strategies

Chapter twenty-three: Hedgehog Inhibition as an Anti-Cancer Strategy

I. Introduction

II. Hh Signaling in Normal Development

III. Hh Pathway Alterations in Cancer

IV. Targeted Therapies for Hedgehog Dependent Cancers

V. Conclusions and Future Directions

Index