Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms
| Autor: | Yongsoo Kim, Delin Chen, Ziedulla Abdullaev, Wei Gu, Alexander L. Kovalchuk, Jiafang Sun, Herbert C. Morse, Shao Xiang, William C. Cho, Siegfried Janz, Ted A. Torrey, Chen-Feng Qi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
p53
CCCTC-Binding Factor MYC lcsh:Chemistry Mice 0302 clinical medicine Transcriptional regulation Proto-Oncogene Proteins c-myc ARF-BP1 B-cell lymphoma CTCF ARF lcsh:QH301-705.5 Spectroscopy 0303 health sciences biology General Medicine 3. Good health Computer Science Applications Ubiquitin ligase Gene Expression Regulation Neoplastic 030220 oncology & carcinogenesis Signal transduction Signal Transduction Lymphoma B-Cell Ubiquitin-Protein Ligases Catalysis Article Inorganic Chemistry 03 medical and health sciences Downregulation and upregulation Cell Line Tumor Animals Humans Physical and Theoretical Chemistry Molecular Biology 030304 developmental biology Tumor Suppressor Proteins Organic Chemistry HEK 293 cells Wild type Neoplasms Experimental Repressor Proteins HEK293 Cells lcsh:Biology (General) lcsh:QD1-999 biology.protein Cancer research Tumor Suppressor Protein p53 |
| Zdroj: | International Journal of Molecular Sciences; Volume 13; Issue 5; Pages: 6204-6219 International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 13, Iss 5, Pp 6204-6219 (2012) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms13056204 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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