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Genes Dev. 2015 Oct 1;29(19):2022-36. doi: 10.1101/gad.263939.115.

Proliferation of progeria cells is enhanced by lamina-associated polypeptide 2α (LAP2α) through expression of extracellular matrix proteins.

Author information

1
Max F. Perutz Laboratories (MFPL), Department of Medical Biochemistry, Medical University of Vienna, Vienna Biocenter (VBC), A-1030 Vienna, Austria;
2
National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract

Lamina-associated polypeptide 2α (LAP2α) localizes throughout the nucleoplasm and interacts with the fraction of lamins A/C that is not associated with the peripheral nuclear lamina. The LAP2α-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 LAP2α and nucleoplasmic lamins A/C, impaired proliferation, and down-regulation of extracellular matrix components. Surprisingly, contrary to wild-type cells, ectopic expression of LAP2α 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, LAP2α can also regulate extracellular matrix components independently of lamins A/C, which may help explain the proliferation-promoting function of LAP2α in cells expressing progerin.

KEYWORDS:

A-type lamins; Hutchinson Gilford progeria; cell proliferation regulation; extracellular matrix; lamina-associated polypeptide; nuclear lamina; nucleoplasmic lamins

PMID:
26443848
PMCID:
PMC4604344
DOI:
10.1101/gad.263939.115
[Indexed for MEDLINE]
Free PMC Article

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