Proliferation of progeria cells is enhanced by lamina-associated polypeptide 2 alpha (LAP2 alpha) through expression of extracellular matrix proteins

摘要

Lamina-associated polypeptide 2 alpha (LAP2 alpha) localizes throughout the nucleoplasm and interacts with the fraction of lamins A/C that is not associated with the peripheral nuclear lamina. The LAP2 alpha lamin A/C complex negatively affects cell proliferation. Lamins A/C are encoded by LMNA, a single heterozygous mutation of which causes Hutchinson-Gilford progeria syndrome (HGPS). This mutation generates the lamin A variant progerin, which we show here leads to loss of LAP2 alpha and nucleoplasmic lamins A/C, impaired proliferation, and down-regulation of extracellular matrix components. Surprisingly, contrary to wild-type cells, ectopic expression of LAP2 alpha in cells expressing progerin restores proliferation and extracellular matrix expression but not the levels of nucleoplasmic lamins A/C. We conclude that, in addition to its cell cycle-inhibiting function with lamins A/C, LAP2 alpha can also regulate extracellular matrix components independently of lamins A/C, which may help explain the proliferation-promoting function of LAP2 alpha in cells expressing progerin.