Protein kinase C control of gene expression.
Gene expression is fashioned at multiple interconnected levels and is controlled by a complex interplay between nucleosomal assembly, the establishment of multifaceted transcriptional motifs, and the temporal and spatial organization of chromatin in loops and domains. Protein phosphorylation is one of the most versatile posttranslational modifications used in eukaryotic cells and plays a crucial role in the continuous remodeling of different transcriptional regulators. The protein kinase C (PKC) family of serine-threonine kinases encompasses 12 different isozymes that have been shown to transduce a myriad of signals mediated by phospholipid hydrolysis as a consequence of the activation of G protein-coupled receptors, tyrosine kinase receptors, and nonreceptor tyrosine kinases. Although the analysis of PKC activity in many systems has provided crucial insights to its biological function, unraveling the molecular mechanisms that underlie isozyme-specific modulation of gene expression within the complexity of genome structure and function remains a challenging issue. This review focuses on recent advances in PKC-dependent regulation of gene expression within the context of the dynamic linkages involving nuclear architecture and transcription. Implications of isozyme-specific phosphorylation of selected members of transcription factors are also discussed. Future perspectives disclosed by recently available methods for large-scale transcriptional profiling are also outlined.
Ventura
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Department of Biomedical Sciences, University of Sassari, Italy. chim_med@ssmain.uniss.it
Maioli
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D021581:Active Transport, Cell Nucleus; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology; D002467:Cell Nucleus / Q000201:enzymology / Q000648:ultrastructure; D003600:Cytosol / Q000201:enzymology; D004075:Diglycerides / Q000502:physiology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005544:Forecasting; D019204:GTP-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006609:High Mobility Group Proteins / Q000502:physiology; D006657:Histones / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D034882:Lamins; D016350:Leucine Zippers / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000502:physiology; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology; D010703:Phorbol Esters / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000502:physiology; D010743:Phospholipids / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000502:physiology; D016601:RNA-Binding Proteins / Q000502:physiology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D016335:Zinc Fingers / Q000502:physiology; D000097796:Nucleolin
D018797:Cell Cycle Proteins; D004075:Diglycerides; D004791:Enzyme Inhibitors; D019204:GTP-Binding Proteins; D006609:High Mobility Group Proteins; D006657:Histones; D007527:Isoenzymes; D034882:Lamins; D016328:NF-kappa B; D009687:Nuclear Proteins; D010703:Phorbol Esters; D010716:Phosphatidylinositols; D010743:Phospholipids; D010750:Phosphoproteins; D011493:Protein Kinase C; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000097796:Nucleolin; C011439:1,2-diacylglycerol