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大鼠Efp的分子克隆:原代成骨细胞中的表达与调控

Molecular cloning of rat efp: expression and regulation in primary osteoblasts.

作者信息

Inoue S, Urano T, Ogawa S, Saito T, Orimo A, Hosoi T, Ouchi Y, Muramatsu M

机构信息

Department of Biochemistry, Saitama Medical School, 38 Moro-Hongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.

出版信息

Biochem Biophys Res Commun. 1999 Aug 2;261(2):412-8. doi: 10.1006/bbrc.1999.0874.

DOI:10.1006/bbrc.1999.0874
PMID:10425199
Abstract

We have previously identified an estrogen-responsive gene, efp (estrogen-responsive finger protein), by genomic binding-site cloning method. Here, we isolated a rat homologue of efp cDNA that encodes an open reading frame of 644 amino acids sharing high homology with human efp (69% identity at the protein level) and mouse efp (80% identity at the protein level). The efp protein has a RING finger, a variant type of zinc finger motif, B1 box and B2 box, each having a pair of zinc fingers, and coiled-coil domain, belonging to the RING finger-B box-Coiled Coil (RBCC) family. Several members of RBCC family including efp have characteristic C-terminal domain, forming a subfamily. Next, we detected efp mRNA in primary osteoblasts, one of estrogen target cells, derived from the calvariae of rat fetus. An anti-efp antibody revealed the efp protein is expressed and regulated by estrogen in the primary osteoblasts. Interestingly, the efp protein in primary osteoblasts is down-regulated by 1alpha,25-dihydroxyvitamin D(3) treatment that promotes the differentiation of the cells, whereas it is up-regulated by TGF-beta1 treatment that inhibits the differentiation of the cells. These findings suggest the possible involvement of the efp in the differentiation of osteoblastic cells.

摘要

我们先前通过基因组结合位点克隆方法鉴定了一个雌激素反应基因,即efp(雌激素反应性指蛋白)。在此,我们分离出了efp cDNA的大鼠同源物,它编码一个由644个氨基酸组成的开放阅读框,与人类efp(蛋白质水平上69%的同一性)和小鼠efp(蛋白质水平上80%的同一性)具有高度同源性。efp蛋白具有一个RING指结构、一种锌指基序的变体类型、B1框和B2框,每个框都有一对锌指,以及卷曲螺旋结构域,属于RING指-B框-卷曲螺旋(RBCC)家族。包括efp在内的RBCC家族的几个成员具有特征性的C末端结构域,形成一个亚家族。接下来,我们在源自大鼠胎儿颅骨的原代成骨细胞(雌激素靶细胞之一)中检测到了efp mRNA。一种抗efp抗体显示,efp蛋白在原代成骨细胞中由雌激素表达并受其调控。有趣的是,在促进细胞分化的1α,25-二羟基维生素D(3)处理下,原代成骨细胞中的efp蛋白下调,而在抑制细胞分化的TGF-β1处理下,它上调。这些发现表明efp可能参与成骨细胞的分化。

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Oestrogen causes degradation of KLF5 by inducing the E3 ubiquitin ligase EFP in ER-positive breast cancer cells.雌激素通过诱导 ER 阳性乳腺癌细胞中的 E3 泛素连接酶 EFP 导致 KLF5 的降解。
Biochem J. 2011 Jul 15;437(2):323-33. doi: 10.1042/BJ20101388.