title: Proliferation of progeria cells is enhanced by lamina-associated polypeptide 2α (LAP2α) through expression of extracellular matrix proteins.
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.
authors.affiliation: Max F. Perutz Laboratories (MFPL), Department of Medical Biochemistry, Medical University of Vienna, Vienna Biocenter (VBC), A-1030 Vienna, Austria;
authors.forename: Sandra
authors.initials: S
authors.lastname: Vidak
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Nard
authors.initials: N
authors.lastname: Kubben
authors.affiliation: Max F. Perutz Laboratories (MFPL), Department of Medical Biochemistry, Medical University of Vienna, Vienna Biocenter (VBC), A-1030 Vienna, Austria;
authors.forename: Thomas
authors.initials: T
authors.lastname: Dechat
authors.affiliation: Max F. Perutz Laboratories (MFPL), Department of Medical Biochemistry, Medical University of Vienna, Vienna Biocenter (VBC), A-1030 Vienna, Austria;
authors.forename: Roland
authors.initials: R
authors.lastname: Foisner
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011371:Progeria / Q000235:genetics / Q000503:physiopathology*; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; C494847:LMNA protein, human; D034904:Lamin Type A; D008565:Membrane Proteins; C093413:lamina-associated polypeptide 2; C090764:prelamin A
keywords: A-type lamins; Hutchinson Gilford progeria; cell proliferation regulation; extracellular matrix; lamina-associated polypeptide; nuclear lamina; nucleoplasmic lamins