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IGF-1 receptor is down-regulated by sunitinib induces MDM2-dependent ubiquitination
The insulin like growth factor receptor subtype 1(IGF-1R) plays an important role in cancers transformation and progression. The aim is to investigate the effects of sunitinib on IGF-1R cell signaling transduction, especially on receptor phosphorylation and ubiquitination. In HEK293 cells, IGF-1R si...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3642090/ https://www.ncbi.nlm.nih.gov/pubmed/23650573 http://dx.doi.org/10.1016/j.fob.2011.12.001 |
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author | Shen, Hongchang Fang, Yan Dong, Wei Mu, Xueru Liu, Qi Du, Jiajun |
author_facet | Shen, Hongchang Fang, Yan Dong, Wei Mu, Xueru Liu, Qi Du, Jiajun |
author_sort | Shen, Hongchang |
collection | PubMed |
description | The insulin like growth factor receptor subtype 1(IGF-1R) plays an important role in cancers transformation and progression. The aim is to investigate the effects of sunitinib on IGF-1R cell signaling transduction, especially on receptor phosphorylation and ubiquitination. In HEK293 cells, IGF-1R signaling pathways are activated in response to IGF-1, which induces obvious phosphorylations of receptor tyrosine and Akt, ERK. However, the phosphorylations of receptor tyrosine, Akt and ERK were significant inhibited by sunitinib. We found that both IGF-1 and sunitinib obviously down regulated the IGF-1R expression. For analysis the ubiquitination, HEK293 cells were simulated with 100 ng/ml IGF-1 or 10 nM sunitinib for 10 min after serum starvation for 24 h. Both IGF-1 and sunitinib could obviously induce the IGF-1R ubiquitination at 10 min compared with control (only serum free, no stimulation), indicating IGF-1 and sunitinib down-regulate the IGF-1R by increasing the receptor degradation through ubiquitination dependent proteasome pathway. We also found that MDM2 combined to IGF-1R in response to sunitinib stimulation. To confirm it, HEK293 cells were transfected with human HA-MDM2 (+MDM2) or siRNA to MDM2 (−MDM2). Following 24 h serum starvation, cells were stimulated with 10 nM sunitinib for 10 min. In over-expressed MDM2 cells, IGF-1R was more ubiquitinated than that in mock-transfected cells (control), and no ubiquitination in −MDM2 cells. These results mean that sunitinib mediates ubiquitination of IGF-1R dependent on MDM2. In summary, sunitinib could block signaling transduction and mediate degradation of IGF-1R. |
format | Online Article Text |
id | pubmed-3642090 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-36420902013-05-06 IGF-1 receptor is down-regulated by sunitinib induces MDM2-dependent ubiquitination Shen, Hongchang Fang, Yan Dong, Wei Mu, Xueru Liu, Qi Du, Jiajun FEBS Open Bio Article The insulin like growth factor receptor subtype 1(IGF-1R) plays an important role in cancers transformation and progression. The aim is to investigate the effects of sunitinib on IGF-1R cell signaling transduction, especially on receptor phosphorylation and ubiquitination. In HEK293 cells, IGF-1R signaling pathways are activated in response to IGF-1, which induces obvious phosphorylations of receptor tyrosine and Akt, ERK. However, the phosphorylations of receptor tyrosine, Akt and ERK were significant inhibited by sunitinib. We found that both IGF-1 and sunitinib obviously down regulated the IGF-1R expression. For analysis the ubiquitination, HEK293 cells were simulated with 100 ng/ml IGF-1 or 10 nM sunitinib for 10 min after serum starvation for 24 h. Both IGF-1 and sunitinib could obviously induce the IGF-1R ubiquitination at 10 min compared with control (only serum free, no stimulation), indicating IGF-1 and sunitinib down-regulate the IGF-1R by increasing the receptor degradation through ubiquitination dependent proteasome pathway. We also found that MDM2 combined to IGF-1R in response to sunitinib stimulation. To confirm it, HEK293 cells were transfected with human HA-MDM2 (+MDM2) or siRNA to MDM2 (−MDM2). Following 24 h serum starvation, cells were stimulated with 10 nM sunitinib for 10 min. In over-expressed MDM2 cells, IGF-1R was more ubiquitinated than that in mock-transfected cells (control), and no ubiquitination in −MDM2 cells. These results mean that sunitinib mediates ubiquitination of IGF-1R dependent on MDM2. In summary, sunitinib could block signaling transduction and mediate degradation of IGF-1R. Elsevier 2011-12-27 /pmc/articles/PMC3642090/ /pubmed/23650573 http://dx.doi.org/10.1016/j.fob.2011.12.001 Text en © 2012 Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non- commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Article Shen, Hongchang Fang, Yan Dong, Wei Mu, Xueru Liu, Qi Du, Jiajun IGF-1 receptor is down-regulated by sunitinib induces MDM2-dependent ubiquitination |
title | IGF-1 receptor is down-regulated by sunitinib induces MDM2-dependent ubiquitination |
title_full | IGF-1 receptor is down-regulated by sunitinib induces MDM2-dependent ubiquitination |
title_fullStr | IGF-1 receptor is down-regulated by sunitinib induces MDM2-dependent ubiquitination |
title_full_unstemmed | IGF-1 receptor is down-regulated by sunitinib induces MDM2-dependent ubiquitination |
title_short | IGF-1 receptor is down-regulated by sunitinib induces MDM2-dependent ubiquitination |
title_sort | igf-1 receptor is down-regulated by sunitinib induces mdm2-dependent ubiquitination |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3642090/ https://www.ncbi.nlm.nih.gov/pubmed/23650573 http://dx.doi.org/10.1016/j.fob.2011.12.001 |
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