Proteasome-mediated degradation of integral inner nuclear membrane protein emerin in fibroblasts lacking A-type lamins
- Departments of Medicine and Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States)
- Inserm, U582, Institut de Myologie, Paris F-75013 (France)
- Neuromuscular Centre Nijmegen, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)
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-1{alpha} 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.
- OSTI ID:
- 20857943
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 351, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2006.10.147; PII: S0006-291X(06)02411-9; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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