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Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms
Transcriptional activation of MYC is a hallmark of many B cell lineage neoplasms. MYC provides a constitutive proliferative signal but can also initiate ARF-dependent activation of p53 and apoptosis. The E3 ubiquitin ligase, ARF-BP1, encoded by HUWE1, modulates the activity of both the MYC and the A...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International (MDPI)
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382761/ https://www.ncbi.nlm.nih.gov/pubmed/22754359 http://dx.doi.org/10.3390/ijms13056204 |
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author | Qi, Chen-Feng Kim, Yong-Soo Xiang, Shao Abdullaev, Ziedulla Torrey, Ted A. Janz, Siegfried Kovalchuk, Alexander L. Sun, Jiafang Chen, Delin Cho, William C. Gu, Wei Morse, Herbert C. |
author_facet | Qi, Chen-Feng Kim, Yong-Soo Xiang, Shao Abdullaev, Ziedulla Torrey, Ted A. Janz, Siegfried Kovalchuk, Alexander L. Sun, Jiafang Chen, Delin Cho, William C. Gu, Wei Morse, Herbert C. |
author_sort | Qi, Chen-Feng |
collection | PubMed |
description | Transcriptional activation of MYC is a hallmark of many B cell lineage neoplasms. MYC provides a constitutive proliferative signal but can also initiate ARF-dependent activation of p53 and apoptosis. The E3 ubiquitin ligase, ARF-BP1, encoded by HUWE1, modulates the activity of both the MYC and the ARF-p53 signaling pathways, prompting us to determine if it is involved in the pathogenesis of MYC-driven B cell lymphomas. ARF-BP1 was expressed at high levels in cell lines from lymphomas with either wild type or mutated p53 but not in ARF-deficient cells. Downregulation of ARF-BP1 resulted in elevated steady state levels of p53, growth arrest and apoptosis. Co-immunoprecipitation studies identified a multiprotein complex comprised of ARF-BP1, ARF, p53, MYC and the multifunctional DNA-binding factor, CTCF, which is involved in the transcriptional regulation of MYC, p53 and ARF. ARF-BP1 bound and ubiquitylated CTCF leading to its proteasomal degradation. ARF-BP1 and CTCF thus appear to be key cofactors linking the MYC proliferative and p53-ARF apoptotic pathways. In addition, ARF-BP1 could be a therapeutic target for MYC-driven B lineage neoplasms, even if p53 is inactive, with inhibition reducing the transcriptional activity of MYC for its target genes and stabilizing the apoptosis-promoting activities of p53. |
format | Online Article Text |
id | pubmed-3382761 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
spelling | pubmed-33827612012-06-29 Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms Qi, Chen-Feng Kim, Yong-Soo Xiang, Shao Abdullaev, Ziedulla Torrey, Ted A. Janz, Siegfried Kovalchuk, Alexander L. Sun, Jiafang Chen, Delin Cho, William C. Gu, Wei Morse, Herbert C. Int J Mol Sci Article Transcriptional activation of MYC is a hallmark of many B cell lineage neoplasms. MYC provides a constitutive proliferative signal but can also initiate ARF-dependent activation of p53 and apoptosis. The E3 ubiquitin ligase, ARF-BP1, encoded by HUWE1, modulates the activity of both the MYC and the ARF-p53 signaling pathways, prompting us to determine if it is involved in the pathogenesis of MYC-driven B cell lymphomas. ARF-BP1 was expressed at high levels in cell lines from lymphomas with either wild type or mutated p53 but not in ARF-deficient cells. Downregulation of ARF-BP1 resulted in elevated steady state levels of p53, growth arrest and apoptosis. Co-immunoprecipitation studies identified a multiprotein complex comprised of ARF-BP1, ARF, p53, MYC and the multifunctional DNA-binding factor, CTCF, which is involved in the transcriptional regulation of MYC, p53 and ARF. ARF-BP1 bound and ubiquitylated CTCF leading to its proteasomal degradation. ARF-BP1 and CTCF thus appear to be key cofactors linking the MYC proliferative and p53-ARF apoptotic pathways. In addition, ARF-BP1 could be a therapeutic target for MYC-driven B lineage neoplasms, even if p53 is inactive, with inhibition reducing the transcriptional activity of MYC for its target genes and stabilizing the apoptosis-promoting activities of p53. Molecular Diversity Preservation International (MDPI) 2012-05-21 /pmc/articles/PMC3382761/ /pubmed/22754359 http://dx.doi.org/10.3390/ijms13056204 Text en © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Qi, Chen-Feng Kim, Yong-Soo Xiang, Shao Abdullaev, Ziedulla Torrey, Ted A. Janz, Siegfried Kovalchuk, Alexander L. Sun, Jiafang Chen, Delin Cho, William C. Gu, Wei Morse, Herbert C. Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms |
title | Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms |
title_full | Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms |
title_fullStr | Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms |
title_full_unstemmed | Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms |
title_short | Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms |
title_sort | characterization of arf-bp1/huwe1 interactions with ctcf, myc, arf and p53 in myc-driven b cell neoplasms |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382761/ https://www.ncbi.nlm.nih.gov/pubmed/22754359 http://dx.doi.org/10.3390/ijms13056204 |
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