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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 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.

Pubmed ID: 22754359


  • Qi CF
  • Kim YS
  • Xiang S
  • Abdullaev Z
  • Torrey TA
  • Janz S
  • Kovalchuk AL
  • Sun J
  • Chen D
  • Cho WC
  • Gu W
  • Morse HC


International journal of molecular sciences

Publication Data

July 3, 2012

Associated Grants

  • Agency: NCI NIH HHS, Id: P01 CA080058
  • Agency: NCI NIH HHS, Id: P01 CA097403
  • Agency: NCI NIH HHS, Id: R01 CA151354
  • Agency: NCI NIH HHS, Id: R01 CA151354

Mesh Terms

  • Animals
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Lymphoma, B-Cell
  • Mice
  • Neoplasms, Experimental
  • Proto-Oncogene Proteins c-myc
  • Repressor Proteins
  • Signal Transduction
  • Tumor Suppressor Protein p53
  • Ubiquitin-Protein Ligases