Journal article
Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms
International journal of molecular sciences, Vol.13(5), pp.6204-6219
05/2012
DOI: 10.3390/ijms13056204
PMCID: PMC3382761
PMID: 22754359
Abstract
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.
Details
- Title: Subtitle
- Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms
- Creators
- Chen-Feng Qi - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA; E-MailsYong-Soo Kim - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA; E-MailsShao Xiang - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA; E-MailsZiedulla Abdullaev - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA; E-MailsTed A Torrey - Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; E-MailSiegfried Janz - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; E-MailAlexander L Kovalchuk - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA; E-MailsJiafang Sun - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA; E-MailsDelin Chen - Institute for Cancer Genetics, and Department of Pathology and Cell Biology, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA; E-MailsWilliam C Cho - Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China; E-MailWei Gu - Institute for Cancer Genetics, and Department of Pathology and Cell Biology, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA; E-MailsHerbert C Morse - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA; E-Mails
- Resource Type
- Journal article
- Publication Details
- International journal of molecular sciences, Vol.13(5), pp.6204-6219
- Publisher
- Molecular Diversity Preservation International (MDPI)
- DOI
- 10.3390/ijms13056204
- PMID
- 22754359
- PMCID
- PMC3382761
- ISSN
- 1422-0067
- eISSN
- 1422-0067
- Language
- English
- Date published
- 05/2012
- Academic Unit
- Pathology
- Record Identifier
- 9984083832702771
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