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...

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Main Authors:	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.
Format:	Online
Language:	English
Published:	Molecular Diversity Preservation International (MDPI) 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382761/

id	pubmed-3382761
recordtype	oai_dc
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. 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/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
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.
spellingShingle	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
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
title	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_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_sort	characterization of arf-bp1/huwe1 interactions with ctcf, myc, arf and p53 in myc-driven b cell neoplasms
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.
publisher	Molecular Diversity Preservation International (MDPI)
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382761/
_version_	1611538993960189952

Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms

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