論文 - 詳細
RRC ID | 46583 |
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著者 | Darom A, Bening-Abu-Shach U, Broday L. |
タイトル | RNF-121 is an endoplasmic reticulum-membrane E3 ubiquitin ligase involved in the regulation of beta-integrin. |
ジャーナル | Mol Biol Cell |
Abstract |
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 beta 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. |
巻・号 | 21(11) |
ページ | 1788-98 |
公開日 | 2010-6-1 |
DOI | 10.1091/mbc.e09-09-0774 |
PII | E09-09-0774 |
PMID | 20357004 |
PMC | PMC2877638 |
MeSH | Animals Animals, Genetically Modified Caenorhabditis elegans / anatomy & histology Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Endoplasmic Reticulum / enzymology* Gonads / abnormalities Gonads / metabolism Heat-Shock Proteins / genetics Heat-Shock Proteins / metabolism Integrin beta Chains / genetics Integrin beta Chains / metabolism* MAP Kinase Kinase 1 / genetics MAP Kinase Kinase 1 / metabolism RING Finger Domains* RNA Interference Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Signal Transduction / physiology Stress, Physiological Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism* eIF-2 Kinase / genetics eIF-2 Kinase / metabolism |
IF | 3.791 |
引用数 | 27 |
WOS 分野 | CELL BIOLOGY |
リソース情報 | |
線虫 | tm794 |