Novel progerin-interactive partner proteins hnRNP E1, EGF, Mel 18, and UBC9 interact with lamin A/C
Novel progerin-interactive partner proteins hnRNP E1, EGF, Mel 18, and UBC9 interact with lamin A/C
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DOI：
10.1016/j.bbrc.2005.10.020
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发表时间：
2005-12-16
影响因子：
3.1
通讯作者：
Brown, WT
中科院分区：
文献类型：
--
作者：
Zhong, N;Radu, G;Brown, WT
Hutchinson-Gilford progeria syndrome（HGPS或progeria）是一种儿童期明显的加速衰老疾病。最近，HGPS已被表征为一组称为核纤层蛋白病的疾病之一，其由核纤层蛋白A/C（LMNA）基因的遗传缺陷引起。大多数HGPS突变等位基因涉及沉默突变，c.2063C > T导致G608 G，其在LMNA的外显子11中产生隐蔽剪接位点，并因此在前核纤层蛋白A/C的C末端附近截短50个氨基酸。为了探索HGPS发展的可能机制，我们开始使用酵母双杂交系统寻找与早老蛋白（HGPS中截短的核纤层蛋白A）独特相互作用的蛋白质。四个新的早老蛋白相互作用的伙伴蛋白，以前没有发现相互作用的核纤层蛋白A/C：hnRNP E1，UBC 9（泛素结合酶E2 I），梅尔-18，EGF 1。然而，使用对照和早衰症成纤维细胞，内源性蛋白质的免疫共沉淀研究没有显示与正常核纤层蛋白A/C相比的差异结合亲和力。因此，我们没有找到证据，独特的相互作用的伴侣蛋白使用这种方法，但确定了四个新的核纤层蛋白A/C相互作用的合作伙伴。(c)2005年爱思唯尔公司All rights reserved.
The Hutchinson-Gilford progeria syndrome (HGPS or progeria) is an apparent accelerated aging disorder of childhood. Recently, HGPS has been characterized as one of a growing group of disorders known as laminopathies, which result from genetic defects of the lamin A/C (LMNA) gene. The majority of HGPS mutant alleles involve a silent mutation, c.2063C > T resulting in G608G, that generates a cryptic splicing site in exon 11 of LMNA and consequently truncates 50 amino acids near the C-terminus of pre-lamin A/C. To explore possible mechanisms underlying the development of HGPS, we began a search for proteins that would uniquely interact with progerin (the truncated lamin A in HGPS) using a yeast two-hybrid system. Four new progerin interactive partner proteins were identified that had not been previously found to interact with lamin A/C: hnRNP E1, UBC9 (ubiquitin conjugating enzyme E2I), Mel-18, and EGF1. However, using control and progeria fibroblasts, co-immunoprecipitation studies of endogenous proteins did not show differential binding affinity compared to normal lamin A/C. Thus, we did not find evidence for uniquely interacting partner proteins using this approach, but did identify four new lamin A/C interactive partners. (c) 2005 Elsevier Inc. All rights reserved.