Regulatory Networks of Liverenriched Transcription Factors in Liver Biology and Disease 327

Jürgen Borlak, Jürgen Klempnauer, and Harald Schrem

14.1 Introduction 327

14.2 The HNF-1/HNF-4 Network for Liver-specific Gene Expression 328

14.2.1 HNF-1 Regulates HNF-4alpha Expression 329

14.2.2 HNF-1alpha and HNF-4 Regulate HNF-1alpha Expression 329

14.2.3 Dimerization Cofactor of HNF-1alpha and Liver-specific Gene Expression 331

14.2.4 Agonistic and Antagonistic Ligands for the Orphan Nuclear Receptor HNF-4alpha 331

14.2.5 Coactivators for HNF-1 and HNF-4 and Their Network Effects in Liver Biology 334

14.2.6 The Relevance of HNF-4alpha Splice Variants in Differential Transcriptional Regulation 336

14.2.7 Activation and Repression by Homo- and Heterodimerization of HNF-4alpha Proteins 336

14.2.8 Posttranscriptional Modification of HNF-4 Function by Phosphorylation and Acetylation 337

14.2.9 Cooperation and Competition between COUP-TF and HNF-4 337

14.2.10 The Role of HNFs in CYP Monooxygenase Expression 338

14.3 HNF-6 and HNF-3beta in Liver-specific Transcription Factor Networks 339

14.3.1 HNF-6, OC-2, HNF-3beta, and C/EBPs Regulate HNF-3beta Expression 339

14.3.2 Competition and Cooperation between HNF-3alpha and HNF-3beta 340

14.4 The Role of C/EBPs in Diverse Physiological Functions 340

14.4.1 C/EBP-alpha in Energy Metabolism and Detoxification 340

14.4.2 C/EBP-beta in Energy Metabolism 343

14.4.3 C/EBPs in the Acute-phase Response 344

14.4.4 Protein-Protein Interactions of C/EBP-beta during the Acute-phase Response 347

14.4.5 C/EBPs in Liver Regeneration 348

14.4.6 C/EBPs and Apoptosis 349

14.4.7 C/EBPs in Liver Development 350

14.4.8 The Role of C/EBPs in CYP Monooxygenase Expression during Development 350

14.4.9 C/EBPs and Their Role in Liver Tumour Biology 351

14.5 Involvement of C/EBP-alpha and C/EBP-beta in Regulation of Cell Cycle Control 352

14.5.1 C/EBP-alpha Expression and Growth Arrest 352

14.5.2 Glucocorticoid-induced G1 Cell Cycle Arrest Is Mediated by C/EBP-alpha 352

14.5.3 Protein-Protein Interactions between p21, cdk2, cdk4, and C/EBP-alpha 354

14.5.4 C/EBP-alpha and p107 Protein-Protein Interaction Disrupts E2F Complexes 355

14.5.5 C/EBP-beta Arrests the Cell Cycle before the G1/S Boundary 356

14.6 DBP Circadian Gene Regulation in the Liver 356

14.7 Conclusions and Outlook 358 References 360

0 0

Post a comment