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Biochem Biophys Res Commun. 2006 Dec 29;351(4):1011-7. Epub 2006 Nov 3.

Proteasome-mediated degradation of integral inner nuclear membrane protein emerin in fibroblasts lacking A-type lamins.

Author information

1
Departments of Medicine and Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Abstract

We previously identified and characterized a homozygous LMNA nonsense mutation leading to the absence of A-type lamins in a premature neonate who died at birth. We show here that the absence of A-type lamins is due to degradation of the aberrant mRNA transcript with a premature termination codon. In cultured fibroblasts from the subject with the homozygous LMNA nonsense mutation, there was a decreased steady-state expression of the integral inner nuclear membrane proteins emerin and nesprin-1alpha associated with their mislocalization to the bulk endoplasmic reticulum and a hyperphosphorylation of emerin. To determine if decreased emerin expression occurred post-translationally, we treated cells with a selective proteasome inhibitor and observed an increase in expression. Our results show that mislocalization of integral inner nuclear membrane proteins to the endoplasmic reticulum in human cells lacking A-type lamins leads to their degradation and provides the first evidence that their degradation is mediated by the proteasome.

PMID:
17097067
PMCID:
PMC1771114
DOI:
10.1016/j.bbrc.2006.10.147
[Indexed for MEDLINE]
Free PMC Article

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