RNF135, a ring finger protein, promote proliferation of human glioblastoma cells in vivo and in vitro via ERK pathway

ISG15 is an interferon-stimulated, ubiquitin-like protein that can conjugate to substrate proteins (ISGylation) to counteract microbial infection, but the underlying mechanisms remain elusive. Here, we used a viral-like particle trapping technology to identify ISG15-binding proteins and discovered Ring Finger Protein 213 (RNF213) as an ISG15 interactor and cellular sensor of ISGylated proteins. RNF213 is a poorly-characterized, interferon-induced megaprotein that is frequently mutated in Moyamoya disease, a rare cerebrovascular disorder. We found that interferon induces ISGylation and oligomerization of RNF213 on lipid droplets, where it acts as a sensor for ISGylated proteins. We showed that RNF213 has broad antimicrobial activity in vitro and in vivo, counteracting infection with Listeria monocytogenes, herpes simplex virus 1 (HSV-1), human respiratory syncytial virus (RSV) and coxsackievirus B3 (CVB3), and we observed a striking co-localization of RNF213 with intracellular bacteria. Together, our findings provide novel molecular insights into the ISGylation pathway and reveal RNF213 as a key antimicrobial effector.

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Down-regulation of ribosomal protein S15A inhibits proliferation of human glioblastoma cells in vivo and in vitro via AKT pathway

Tumor Biology ◽

10.1007/s13277-015-4323-0 ◽

2015 ◽

Vol 37 (4) ◽

pp. 4979-4990 ◽

Cited By ~ 11

Author(s):

Yiqun Yao ◽

Yongjian Liu ◽

Xiupeng Lv ◽

Bin Dong ◽

Feng Wang ◽

...

Keyword(s):

Ribosomal Protein ◽

Akt Pathway ◽

Glioblastoma Cells ◽

Down Regulation ◽

Human Glioblastoma ◽

Human Glioblastoma Cells

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Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity

Nature Communications ◽

10.1038/s41467-021-26061-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Fabien Thery ◽

Lia Martina ◽

Caroline Asselman ◽

Yifeng Zhang ◽

Madeleine Vessely ◽

...

Keyword(s):

Antimicrobial Activity ◽

Ring Finger ◽

Ring Finger Protein ◽

Microbial Infection ◽

Herpes Simplex Virus 1 ◽

Finger Protein ◽

Syncytial Virus ◽

Simplex Virus

AbstractISG15 is an interferon-stimulated, ubiquitin-like protein that can conjugate to substrate proteins (ISGylation) to counteract microbial infection, but the underlying mechanisms remain elusive. Here, we use a virus-like particle trapping technology to identify ISG15-binding proteins and discover Ring Finger Protein 213 (RNF213) as an ISG15 interactor and cellular sensor of ISGylated proteins. RNF213 is a poorly characterized, interferon-induced megaprotein that is frequently mutated in Moyamoya disease, a rare cerebrovascular disorder. We report that interferon induces ISGylation and oligomerization of RNF213 on lipid droplets, where it acts as a sensor for ISGylated proteins. We show that RNF213 has broad antimicrobial activity in vitro and in vivo, counteracting infection with Listeria monocytogenes, herpes simplex virus 1, human respiratory syncytial virus and coxsackievirus B3, and we observe a striking co-localization of RNF213 with intracellular bacteria. Together, our findings provide molecular insights into the ISGylation pathway and reveal RNF213 as a key antimicrobial effector.

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Long-term In Vitro Treatment of Human Glioblastoma Cells with Temozolomide Increases Resistance In Vivo through Up-regulation of GLUT Transporter and Aldo-Keto Reductase Enzyme AKR1C Expression

Neoplasia ◽

10.1593/neo.10526 ◽

2010 ◽

Vol 12 (9) ◽

pp. 727-739 ◽

Cited By ~ 60

Author(s):

Benjamin Le Calvé ◽

Michal Rynkowski ◽

Marie Le Mercier ◽

Céline Bruyère ◽

Caroline Lonez ◽

...

Keyword(s):

Glioblastoma Cells ◽

Human Glioblastoma ◽

Human Glioblastoma Cells ◽

In Vitro Treatment

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RNF5, a RING Finger Protein That Regulates Cell Motility by Targeting Paxillin Ubiquitination and Altered Localization

Molecular and Cellular Biology ◽

10.1128/mcb.23.15.5331-5345.2003 ◽

2003 ◽

Vol 23 (15) ◽

pp. 5331-5345 ◽

Cited By ~ 66

Author(s):

Christine Didier ◽

Limor Broday ◽

Anindita Bhoumik ◽

Sharon Israeli ◽

Shoichi Takahashi ◽

...

Keyword(s):

Cell Motility ◽

Ring Finger ◽

Focal Adhesions ◽

Normal Growth ◽

Ring Finger Protein ◽

C Elegans ◽

Amino Terminal ◽

Finger Protein

ABSTRACT RNF5 is a RING finger protein found to be important in the growth and development of Caenorhabditis elegans. The search for RNF5-associated proteins via a yeast two-hybrid screen identified a LIM-containing protein in C. elegans which shows homology with human paxillin. Here we demonstrate that the human homologue of RNF5 associates with the amino-terminal domain of paxillin, resulting in its ubiquitination. RNF5 requires intact RING and C-terminal domains to mediate paxillin ubiquitination. Whereas RNF5 mediates efficient ubiquitination of paxillin in vivo, protein extracts were required for in vitro ubiquitination, suggesting that additional modifications and/or an associated E3 ligase assist RNF5 targeting of paxillin ubiquitination. Mutant Ubc13 efficiently inhibits RNF5 ubiquitination, suggesting that RNF5 generates polychain ubiquitin of the K63 topology. Expression of RNF5 increases the cytoplasmic distribution of paxillin while decreasing its localization within focal adhesions, where it is primarily seen under normal growth. Concomitantly, RNF5 expression results in inhibition of cell motility. Via targeting of paxillin ubiquitination, which alters its localization, RNF5 emerges as a novel regulator of cell motility.

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