Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2012
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
_version_ 1782236542220107776
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
work_keys_str_mv AT qichenfeng characterizationofarfbp1huwe1interactionswithctcfmycarfandp53inmycdrivenbcellneoplasms
AT kimyongsoo characterizationofarfbp1huwe1interactionswithctcfmycarfandp53inmycdrivenbcellneoplasms
AT xiangshao characterizationofarfbp1huwe1interactionswithctcfmycarfandp53inmycdrivenbcellneoplasms
AT abdullaevziedulla characterizationofarfbp1huwe1interactionswithctcfmycarfandp53inmycdrivenbcellneoplasms
AT torreyteda characterizationofarfbp1huwe1interactionswithctcfmycarfandp53inmycdrivenbcellneoplasms
AT janzsiegfried characterizationofarfbp1huwe1interactionswithctcfmycarfandp53inmycdrivenbcellneoplasms
AT kovalchukalexanderl characterizationofarfbp1huwe1interactionswithctcfmycarfandp53inmycdrivenbcellneoplasms
AT sunjiafang characterizationofarfbp1huwe1interactionswithctcfmycarfandp53inmycdrivenbcellneoplasms
AT chendelin characterizationofarfbp1huwe1interactionswithctcfmycarfandp53inmycdrivenbcellneoplasms
AT chowilliamc characterizationofarfbp1huwe1interactionswithctcfmycarfandp53inmycdrivenbcellneoplasms
AT guwei characterizationofarfbp1huwe1interactionswithctcfmycarfandp53inmycdrivenbcellneoplasms
AT morseherbertc characterizationofarfbp1huwe1interactionswithctcfmycarfandp53inmycdrivenbcellneoplasms