| Lamins and lamin associated proteins are the major components of nuclear lamina found between the inner nuclear membrane and the peripheral chromatin. These proteins play important roles in maintaining nuclear structure, chromatin organization, DNA replication, cell cycle regulation, and apoptosis. Lamins are type V intermediate filaments that are further classified into type A and type B lamin proteins. Type A lamins (including lamin A and the smaller lamin C splice variant) are predominately expressed in terminally differentiated cells, whereas type B lamins (lamin B1, lamin B2) are encoded by distinct genes and are expressed constitutively. Cleavage of lamins by caspases occurs during apoptosis as part of the disassembly of the cell. A number of lamina-associated proteins contribute to the nuclear lamina and include the lamin B receptor, LAP1, LAP2, emerin, MAN1, otefin, and YA. Several isoforms of lamina-associated polypeptide 2 (LAP2, also known as thymopoietin or TMPO) have been described, with the α, β, and γ isoforms most abundant in humans. Structurally similar LAP2β and LAP2γ are type II integral membrane proteins. LAP2α has a unique carboxy-terminus that lacks a transmembrane region and results in localization of LAP2α throughout the nucleus where it can associate with lamin A/C. LAP2α is also thought to contribute to the nuclear anchorage of retinoblastoma protein (Rb) and control cell cycle progression. LAP2α is also targeted for cleavage by caspases, which may contribute to changes in chromatin structure during apoptosis. |
