Nuclear lamins: Key regulators of nuclear structure and activities

The lamin molecule Domain organization of lamins Lamins are divided to type A and type B Post-translational processing of lamin molecules Lamin molecules in evolution The supramolecular assembly of lamins From lamin monomer to lamin dimer From dimers to filaments The roles of the different domains in the assembly of lamins Laminopathic mutations affect lamin filament assembly Lamin assembly in vivo Lamin-binding proteins Lamins, chromatin and epigenesis Lamin binding to DNA Lamin binding to chromatin Lamins affect chromatin organization and epigenesis Lamins are involved in many nuclear functions Lamins determine the shape and stiffness of the nucleus Lamins and DNA replication Lamins in transcription and splicing Lamins and aging Lamins and laminopathies Mutations in lamins and their associated proteins causing 'laminopathies' Animal models for laminopathies Molecular models for laminopathies Lamins and stem cells The Notch pathway The Wnt/β-catenin pathway Other pathways Lamins and cancer Lamins as biomarkers for cancer Lamins and cancer regulating pathways Lamins and cancer related aneuploidy Lamin and viruses Abstract The nuclear lamina is a proteinaceous structure located underneath the inner nuclear membrane (INM), where it associates with the peripheral chromatin. It contains lamins and lamin-associated proteins, including many integral proteins of the INM, chromatin modifying proteins, transcriptional repressors and structural proteins. A fraction of lamins is also present in the nucleoplasm, where it forms stable complexes and is associated with specific nucleoplasmic proteins. The lamins and their associated proteins are required for most nuclear activities, mitosis and for linking the nucleoplasm to all major cytoskeletal networks in the cytoplasm. Mutations in nuclear lamins and their associated proteins cause about 20 different diseases that are collectively called laminopathies'. This review concentrates mainly on lamins, their structure and their roles in DNA replication, chromatin organization, adult stem cell differentiation, aging, tumorogenesis and the lamin mutations leading to laminopathic diseases.