RNF-121 is an endoplasmic reticulum-membrane E3 ubiquitin ligase involved in the regulation of beta-integrin.
RNF-121 is an endoplasmic reticulum-membrane E3 ubiquitin ligase involved in the regulation of beta-integrin.
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DOI：
10.1091/mbc.e09-09-0774
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发表时间：
2010-06-01
影响因子：
3.3
通讯作者：
Broday L
中科院分区：
文献类型：
--
作者：
Darom A;Bening-Abu-Shach U;Broday L
RNF-121是一种E3连接酶环指蛋白，定位于秀丽隐杆线虫内质网，并在UPR和ERAD途径中发挥作用。异二聚体整合素受体的β亚基被鉴定为RNF-121的底物，这表明ERAD通过调节β-整合素与细胞粘附之间存在联系。我们报道了一种进化保守的E3连接酶环指蛋白RNF-121的特征，该蛋白在秀丽隐杆线虫的各种细胞和组织的内质网（ER）中表达。RNF-121的失活诱导了BiP表达的升高，并增加了蠕虫对内质网应激的敏感性。遗传分析表明RNF-121位于未折叠蛋白反应（UPR）调节蛋白激酶样内质网激酶（PERK）的下游。我们发现PAT-3::GFP，异二聚体整合素受体的β亚基，作为RNF-121底物；虽然诱导RNF-121表达降低了性腺远端尖端细胞中PAT-3::GFP的水平，但抑制RNF-121导致稳定结合的PAT-3::GFP内含物的积累。相应地，在性腺发育的早期阶段，RNF-121的过度表达导致生殖系发育和性腺迁移的异常，这与PAT-3失活后观察到的异常重叠。这些性腺异常的形成需要功能性er相关降解（ERAD）机制。我们的研究发现，RNF-121是一种er锚定的泛素连接酶，通过将其与细胞粘附整合素受体的调节联系起来，在ERAD途径中发挥特定作用。
RNF-121 is an E3 ligase RING finger protein that is localized to the ER in Caenorhabditis elegans and functions in the UPR and ERAD pathways. The β subunit of the heterodimeric integrin receptor was identified as a substrate for RNF-121, suggesting a link between ERAD and cell adhesion through the regulation of β-integrin. We report on the characterization of RNF-121, an evolutionarily conserved E3 ligase RING finger protein that is expressed in the endoplasmic reticulum (ER) of various cells and tissues in Caenorhabditis elegans. Inactivation of RNF-121 induced an elevation in BiP expression and increased the sensitivity of worms to ER stress. Genetic analysis placed RNF-121 downstream of the unfolded protein response (UPR) regulator protein kinase-like endoplasmic reticulum kinase (PERK). We identify PAT-3::GFP, the β subunit of the heterodimeric integrin receptors, as an RNF-121 substrate; whereas induction of RNF-121 expression reduced the level of PAT-3::GFP in the gonad distal tip cells, inhibition of RNF-121 led to the accumulation of stably bound PAT-3::GFP inclusions. Correspondingly, overexpression of RNF-121 during early stages of gonad development led to aberrations in germline development and gonad migration that overlap with those observed after PAT-3 inactivation. The formation of these gonad abnormalities required functional ER-associated degradation (ERAD) machinery. Our findings identify RNF-121 as an ER-anchored ubiquitin ligase that plays a specific role in the ERAD pathway by linking it to the regulation of the cell adhesion integrin receptors.
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DOI：
10.1083/jcb.124.4.491
发表时间：
1994-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hresko MC;Williams BD;Waterston RH
通讯作者：
Waterston RH
影响因子：
4.1
作者：
KOIVISTO, L;HEINO, J;LARJAVA, H
通讯作者：
LARJAVA, H
影响因子：
4.8
作者：
David, Yael;Ziv, Tamar;Navon, Ami
通讯作者：
Navon, Ami
影响因子：
64.8
作者：
Calfon, M;Zeng, HQ;Ron, D
通讯作者：
Ron, D
ER结合的环手指蛋白5（RNF5/RMA1）在转基因小鼠中引起退化性肌病，并在包容体肌炎中受管制。
影响因子：
3.7
作者：
Delaunay, Agnes;Bromberg, Kenneth D.;Hayashi, Yukiko;Mirabella, Massimiliano;Burch, Denise;Kirkwood, Brian;Serra, Carlo;Malicdan, May C.;Mizisin, Andrew P.;Morosetti, Roberta;Broccolini, Aldobrando;Guo, Ling T.;Jones, Stephen N.;Lira, Sergio A.;Puri, Pier Lorenzo;Shelton, G. Diane;Ronai, Ze'ev
通讯作者：
Ronai, Ze'ev