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J Cell Sci. 2018 Feb 8;131(3). pii: jcs208462. doi: 10.1242/jcs.208462.

Nucleoplasmic lamins define growth-regulating functions of lamina-associated polypeptide 2α in progeria cells.

Author information

1
Max F. Perutz Laboratories (MFPL), Center of Medical Biochemistry, Medical University of Vienna, Vienna Biocenter (VBC), Dr. Bohr-Gasse 9, A-1030 Vienna, Austria.
2
Max F. Perutz Laboratories (MFPL), Center of Medical Biochemistry, Medical University of Vienna, Vienna Biocenter (VBC), Dr. Bohr-Gasse 9, A-1030 Vienna, Austria roland.foisner@meduniwien.ac.at.

Abstract

A-type lamins are components of the peripheral nuclear lamina but also localize in the nuclear interior in a complex with lamina-associated polypeptide (LAP) 2α. Loss of LAP2α and nucleoplasmic lamins in wild-type cells increases cell proliferation, but in cells expressing progerin (a mutant lamin A that causes Hutchinson-Gilford progeria syndrome), low LAP2α levels result in proliferation defects. Here, the aim was to understand the molecular mechanism governing how relative levels of LAP2α, progerin and nucleoplasmic lamins affect cell proliferation. Cells from progeria patients and inducible progerin-expressing cells expressing low levels of progerin proliferate faster than wild-type or lamin A-expressing control cells, and ectopic expression of LAP2α impairs proliferation. In contrast, cells expressing high levels of progerin and lacking lamins in the nuclear interior proliferate more slowly, and ectopic LAP2α expression enhances proliferation. However, simultaneous expression of LAP2α and wild-type lamin A or an assembly-deficient lamin A mutant restored the nucleoplasmic lamin A pool in these cells and abolished the growth-promoting effect of LAP2α. Our data show that LAP2α promotes or inhibits proliferation of progeria cells depending on the level of A-type lamins in the nuclear interior.This article has an associated First Person interview with the first author of the paper.

KEYWORDS:

Cell proliferation; LAP2α; Lamin A; Nucleoplasmic lamins; Premature aging; Progeria

PMID:
29361532
PMCID:
PMC5826045
DOI:
10.1242/jcs.208462
[Indexed for MEDLINE]
Free PMC Article

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