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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...

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Autores principales: Shen, Hongchang, Fang, Yan, Dong, Wei, Mu, Xueru, Liu, Qi, Du, Jiajun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2011
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.
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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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