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Article

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

1
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
2
Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
3
Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
4
Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
5
Institute for Cancer Genetics, and Department of Pathology and Cell Biology, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA
6
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2012, 13(5), 6204-6219; https://doi.org/10.3390/ijms13056204
Received: 22 March 2012 / Revised: 24 April 2012 / Accepted: 9 May 2012 / Published: 21 May 2012
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
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. View Full-Text
Keywords: ARF-BP1; B-cell lymphoma; p53; MYC; CTCF; ARF ARF-BP1; B-cell lymphoma; p53; MYC; CTCF; ARF
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MDPI and ACS Style

Qi, C.-F.; Kim, Y.-S.; Xiang, S.; Abdullaev, Z.; Torrey, T.A.; Janz, S.; Kovalchuk, A.L.; Sun, J.; Chen, D.; Cho, W.C.; Gu, W.; Morse III, H.C. Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms. Int. J. Mol. Sci. 2012, 13, 6204-6219. https://doi.org/10.3390/ijms13056204

AMA Style

Qi C-F, Kim Y-S, Xiang S, Abdullaev Z, Torrey TA, Janz S, Kovalchuk AL, Sun J, Chen D, Cho WC, Gu W, Morse III HC. Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms. International Journal of Molecular Sciences. 2012; 13(5):6204-6219. https://doi.org/10.3390/ijms13056204

Chicago/Turabian Style

Qi, Chen-Feng, Yong-Soo Kim, Shao Xiang, Ziedulla Abdullaev, Ted A. Torrey, Siegfried Janz, Alexander L. Kovalchuk, Jiafang Sun, Delin Chen, William C. Cho, Wei Gu, and Herbert C. Morse III. 2012. "Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms" International Journal of Molecular Sciences 13, no. 5: 6204-6219. https://doi.org/10.3390/ijms13056204

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